In a randomized, controlled double-blind study, 15 patients with AIDS-related complex/Walter-Reed 5 (ARC/WR5) were compared during 6 months intravenous immunoglobulin (IVIG) treatment (0.4g/kg body weight every 2 weeks) with 15 placebo-treated patients. This study was aimed at the lymphocyte response to T and B cell mitogens and antigens. 3H-thymidine uptake was determined after stimulation with the unspecific mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), formalinized Staphylococcus aureus-Cowan I (SAC), and with the antigens tuberculin and herpes simplex virus (HSV) at the onset, on days 85, 183, 267 and 351; IgG and IgM antibodies against HSV were measured by ELISA. In addition, 30 untreated HIV-negative controls were tested. For the T cell mitogen PHA, T-cell-dependent B cell mitogen PWM and B cell mitogen SAC, no differences between the two patient groups were observed before therapy nor in the course of therapy or the 6-month observation period thereafter. The entire patient group showed significantly impaired mitogenic response on day 1 as compared to the controls. There was no significant difference in response to tuberculin between the patients and HIV-negative controls, nor for both patients groups before and in the course of treatment. All patients had IgG antibodies against HSV. Three of them showed blastogenie lymphocyte response to HSV on day 1. Among 19 seropositive controls, 7 individuals showed positive HSV lymphocyte response; but for both patient groups, there was no significant difference before and in the course of the treatment and observation period. We concluded that, in spite of some clinical improvement regarding fever and fatigue during IVIG treatment of ARC/WR5 patients, there is no influence on lymphocyte function, as measured by response to mitogens and antigens.