Clinical, microbiological, and lifestyle patterns in homosexual men showing in vitro immunological abnormalities were studied and related to the susceptibility to human T-lymphotropic virus type III (HTLV-III) infection. In a cohort of male homosexual volunteers in Finland, 90% were HTLV-III antibody negative. Ten % of the HTLV-III negative cases showed decreased T-helper/suppressor cell ratios, mostly due to elevated numbers of T-suppressor cells. In this immunosuppressed group, more signs of diarrhea, intestinal giardiasis, genital warts, and hepatitis B were observed than in the other HTLV-III antibody-negative study subjects. The type of sexual practice was not associated with the in vitro immune abnormalities. During a follow-up of up to 16 months, 4 initially HTLV-III antibody negative cases showed seroconversion. Three of these had inverted T-helper/suppressor cell ratios prior to the seroconversion. It is concluded that persons showing in vitro immunosuppression are more susceptible to HTLV-III infection when being exposed to the virus or else alteration in T-cell subsets signals a pre-antibody-positive or early phase of HTLV-III infection.