In the summer of 1965, a female Dalmatian was stolen from a farm in Pennsylvania. Her story changed America.

But the constancies of his daily life were more striking than these other developments. In all the time I'd been gone, Clayton had lived in the same room, on the same feeding schedule, and with many of the same neighbors. Since we'd last seen each other, I'd moved across the country twice, quit graduate school, and become a journalist. Scientists had published more than 10,000 research papers using macaque models, and a team at the Baylor College of Medicine sequenced the entire genome of the rhesus monkey. For Clayton, though, nothing has changed. Every day or two, he's carted off to a room painted all in black, and his head is fixed in place by the post that still protrudes from his skull. He sits there as always, staring at targets on a computer screen. When he moves his eyes the way he's supposed to, he gets a droplet of Tang as a reward.

It occurred to me that Pepper had been lucky. She'd spent her life roaming an 82-acre farm in Slatington, Pa., with a mate, Fred. (They even had a litter of puppies.) Her time at Montefiore Hospital in the summer of 1965 would last all of one day: After a single night spent locked in the rooftop kennel, she was brought downstairs, anesthetized, and killed.

Clayton was born in a breeding center; he grew up in metal boxes and spent his adolescence with a hole in his head and a coil around his eye. In 10 or 15 years of life, he suffered through multiple surgeries and infections and endless hours of restraint in a plastic chair. And for what? Pepper's death, at least, contributed to the development of the cardiac pacemaker—a revolutionary medical device that would prolong millions of lives. Every hour of Clayton's existence has been spent, and will continue to be spent, in the service of basic science.

"Yep, he's still going strong," my former mentor said when I returned from the monkey room. We stood outside a recording chamber, where another animal now sat in front of the monitor. Some people might not like the idea of a monkey working so long, he continued; they say it's better to use each lab animal for one experiment only or a series of related ones … but all the experiments in a given lab are at least somewhat related. "You could easily argue," he added, that the resources necessary to buy and train a new monkey would be a net minus for animal welfare. Why should we euthanize Clayton and start over? Isn't it better for science, and more humane, to use just one animal?

That sort of moral calculus had driven me away from animal research. (I quit in 2003 after a grisly series of experiments involving a suction tube, a scalpel, and the exposed brains of a half-dozen small birds.) Does the cumulative suffering of one animal over 10 years amount to more than the summed misery of several others, used only briefly? Are we trying to reduce the total amount of pain inflicted on animals or the total number of animals killed? Now it seems to me we've grown ever more removed from these sorts of questions.

The development of animal protections has surely reduced suffering in the laboratory. Yet our safeguards have also served to quarantine the ethical debate. The protocols for painful experiments are approved by institutional committees, and the welfare of lab animals has become a topic for obscure scientific measurements. Few outside science get to see what happens inside the laboratory or consider its costs and benefits. (My recent visit with Clayton was itself unusual; primate labs are rarely so welcoming to members of the press.

Pepper brought us through the laboratory door 40 years ago and generated enough public engagement to pass the Animal Welfare Act. Someone's pet—a member of the family—had gotten lost in the enormous enterprise of biomedicine, and we all went in after her. But scientists today no longer need to pluck stray dogs from country roads. Today's lab animals are professionals—life-long civil servants like Clayton, toiling away in the back rooms of a public institution; or else they're disposable commodities, like the millions of rats and mice that ship out from breeding centers every year. Theirs is a closed ecosystem of universities, hospitals, and breeders—a world behind doors with electronic locks.

Will anyone bother to look inside?

Correction, June 9, 2009: This article originally referred to Pavlov's discovery that "animals would drool at the sound of a bell." That's a widely held misconception about his work. It was already well-known that animals could learn to salivate in response to sounds; Pavlov helped elucidate the meaning and function of these conditioned reflexes. References to a "bell" in his work are the result of a long-standing mistranslation from the Russian of the word for "electrical buzzer." In fact, Pavlov only used a bell once or twice in more than 30 years of research. (Return  to the corrected sentence.)

Correction, June 11, 2009: The original version described iron supplements as a cure for pernicious anemia. It was the vitamin B12 in liver that served as the basis for Whipple's cure. His experimental dogs did have an iron deficiency, however.) (Return  to the corrected sentence.)