An open phase 1 study comparing two daily doses of oral ribavirin (1200 and 1600 mg) for 12 weeks was conducted at a single site. Eight human immunodeficiency virus (HIV)-infected adult men with lymphadenopathy or early AIDS-related complex (ARC) symptoms were enrolled in each treatment group. No anti-HIV effect was observed as evaluated by coculture of patients' peripheral blood mononuclear cells or by the level of serum p24 antigenemia. Neither enhancement of two functional lymphocyte markers (specific antigen-induced blastogenesis or interferon-gamma production) nor reduction in serum beta 2-microglobulins was noted. Mild clinical adverse reactions and anemia were observed in both treatment groups. Significant reductions in total lymphocytes, T lymphocytes (CD2 cells), and T lymphocyte subsets (CD4 and CD8 cells) were most notable in the 1600-mg group. Reduction in the lymphocyte populations was most likely due to a direct ribavirin lymphotoxic effect. These observations indicate that ribavirin had no demonstrable beneficial effect on virologic or immunologic HIV surrogate markers at daily doses associated with adverse reactions.