The purposes of this study were 2-fold: (i) To enumerate peripheral immunoregulatory T cell subsets in untreated patients with chronic hepatitis B virus (HBV) infection and (ii) to examine the relationship between disturbances in the balance of lymphocyte subsets with liver disease and the presence of homosexuality. Circulating T lymphocyte subsets were evaluated by monoclonal antibodies to the following cell antigens: OKT3 (total T cells), OKT4 (helper/inducer T cells), and OKT8 (suppressor/cytotoxic T cells). The following groups of subjects were examined: (i) 16 heterosexuals with HBV-associated chronic active hepatitis (CAHB); (ii) 10 heterosexual, healthy HBsAg carriers, and (iii) 16 male homosexuals with CAHB. Controls included 51 healthy heterosexuals and 12 healthy, noninfected male homosexuals. We were able to demonstrate that heterosexuals with CAHB had T4/T8 ratios which did not differ from those of noninfected heterosexuals. Both healthy carriers and healthy homosexuals, however, exhibited significantly lower T4/T8 ratios than did noninfected heterosexuals (p less than 0.05, p less than 0.01, respectively). In addition, homosexuals with CAHB had lower (1.5 +/- 0.1) T4/T8 ratios than did heterosexuals with CAHB (2.0 +/- 0.2). A possible mechanism for these findings is discussed. The data indicate that the presence of homosexuality may be an important factor to consider when evaluating immunoregulatory subsets in CAHB.