To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.