"Let's put it this way: I'm tired," William Masters, 79, told the St Louis Post-Dispatch.
Mr Masters, who was divorced from co-researcher Virginia Johnson, his second wife, in 1992, said he will close the Missouri clinic today. He and his third wife will spend their retirement at a winter home in Arizona and a summer place in upstate New York, he said.
"I'll be doing some writing and lecturing but no more therapy, no more research," he told the newspaper.
Mr Masters, a gynaecologist, won permission in 1954 from Washington University in St Louis to set up a laboratory to study how human sexual response works.
Over the years he and Ms Johnson observed hundreds of men and women - prostitutes and surrogate partners included - in a laboratory during intercourse and masturbation.
Their Human Sexual Response published in 1966 was a best seller, as was their Human Sexual Inadequacy published in 1970.
The couple developed new clinical prescriptions for treating such sexual problems as frigidity, impotency and premature ejaculation.
Mr Masters told the Post-Dispatch his biggest disappointment was that much of the so-called sexual revolution consisted of old myths wrapped in new terminology.
"Sex within a committed relationship is the best non-verbal means of communication that we know of," he said. "We're talking about sex so much more but we're still spending a lot of time perpetuating misperceptions . I wish I knew of a way to stop it," he said."
He said his biggest accomplishment may be that people can talk more openly about sex now. Mr Masters said the early reaction when his research first became public was a flood of mail, much of it telling him and his co-researcher to "drop dead".