To help clarify the nature and pathogenesis of the syndrome of severely opportunistic infection associated with immune deficiency in young homosexual males, we investigated the immunological characteristics of a group of 33 young homosexual men. These young men all had the prodrome to the syndrome which included a history of multiple sexual partners and multiple sexually transmitted diseases. In addition, they all had a past history of mild to moderate viral, bacterial, parasitic, or fungal infections and had used recreational drugs. Within this group of patients, there were five men who had Kaposi's sarcoma. Compared to the 21 normal heterosexual individuals, the homosexual men were found to be anergic to a battery of recall antigens (52% versus 19%); to be hyporesponsive to mitogen stimulation (pokeweed, 30.7 x 10(-3) versus 65.3 x 10(-3) cpm, p less than or equal to 0.005; concanavalin A, 32.2 x 10(-3) versus 60.1 x 10(-3) cpm, p less than or equal to 0.006); and to have lower helper T-cells (18% versus 34.6%, p less than or equal to 0.01), inverted helper:suppressor T-cell ratios (0.85 versus 1.92, p less than or equal to 0.01), and an elevated serum thymosin alpha 1 level (1473 versus 524 pg/ml, p less than or equal to 0.001). These data suggest that the immunological defect precedes the syndrome. The mechanism of this phenomenon is unclear; however, the repeated viral infection combined with drug usage may be responsible. The five patients with Kaposi's sarcoma were compared as a group to the other patients without cancer and found to be more severely immunodeficient. This suggests that the immune suppression by the malignant disease is superimposed on the preexisting deficiency.