The pertinent clinical data and histologic features of the testes in 57 autopsied acquired immunodeficiency syndrome (AIDS) patients were analyzed and compared with those of 55 age-matched control patients without AIDS. The testes of the AIDS patients showed a significantly lower degree of spermatogenesis (determined by a testicular score count), as well as more prominent thickening of the basement membrane and interstitial fibrosis when compared with the controls. While the precise cause of testicular atrophy in AIDS patients remains to be determined, the chronicity of the disease, prolonged fever, malnutrition, testicular infection, and chemotherapy are all contributing factors. Since the vast majority of the studied AIDS patients were homosexual and most control patients were heterosexual, the observed testicular changes can be ascribed to AIDS and/or homosexuality. Because of a high prevalence of sexually transmitted diseases, antisperm antibodies, and possible zinc deficiency and endocrine disorders, homosexual men appear predisposed to tubular atrophy. Conversely, AIDS-related factors, such as a direct toxic effect of the human immunodeficiency virus on germinal epithelium or as yet undetermined endocrine imbalances might exert a detrimental effect on the testis independent of homosexuality.