The Sydney AIDS Project is a prospective immunoepidemiological study of 911 homosexual and bisexual men enrolled between February 1984 and January 1985. Clinical, immunological, and serological studies are performed on these subjects every six months. At enrollment, 39.9% of subjects were seropositive for antibodies to AIDS retrovirus (ARV). Of these 352 seropositive subjects, 28.1% were symptomless with normal immune profiles, 23.6% were symptomless with an immunodeficiency, 18.8% had a clinical illness but normal immune profile, and 29.6% had a clinical illness and immunodeficiency. Of the symptomless subjects, 27.8% were seropositive for antibodies to ARV. Clinically, seropositivity was significantly associated with enlargement of three or more non-inguinal lymph node groups, splenomegaly, and hepatomegaly. Immunologically, seropositivity was significantly associated with lower absolute numbers of lymphocytes and T4+ lymphocytes and a lower T4+ : T8+ ratio, compared with seronegative subjects. Seropositive subjects with a clinical illness had a significantly lower percentage of T4+ lymphocytes and lower T4+ : T8+ ratio than did those who were symptomless. However, the absolute number of T4+ cells was not significantly different between subjects with a clinical illness and those who were symptomless. Subjects whose sera were positive by immunofluorescence and enzyme-linked immunosorbent assay but were negative by radioimmune precipitation assay had a lower number and percentage of T4+ lymphocytes than subjects who were positive by all three tests. These results demonstrate a wide variety of clinical and immunological responses to ARV infection. Prospective study of these subjects will enable us to define further the natural history of ARV infection and factors associated with progression.