In this study we evaluated interleukin-6 (IL-6) plasma levels in 80 human immunodeficiency virus type 1 (HIV-1) seropositive (+) individuals and 51 HIV-1 seronegative (-) blood donors. Plasma IL-6, detectable only in a subset of HIV-1(+) individuals (45 of 80) and normal blood donors (28 of 51), was significantly (p less than 0.01) increased in HIV-1(+) subjects 187 +/- 20.5 vs. 86.3 +/- 14 pg/ml). Among HIV-1-infected individuals, ARC/AIDS patients showed the highest IL-6 values (243.3 +/- 43.3 pg/ml). HIV-1(+) subjects showed, at all the different stages of the disease, a significant increase in total gammaglobulins, particularly IgG (2071 +/- 101 vs 1265 +/- 34 of HIV-1 seronegative controls). Although among HIV-1-infected individuals, the group with detectable plasma levels of IL-6 shows the highest levels of IgG (2243 +/- 146 vs. 1790 +/- 105, p less than 0.05), no positive correlations were observed between plasma levels of IL-6 and total gamma globulins (r = 0.2) or IgG (0.17). IL-6 production was also examined in the endotoxin-free supernatants of peripheral blood cultured monocytes and CD4+ T lymphocytes, in the presence or absence of specific stimuli. The amount of IL-6 released in monocyte and CD4+ T-lymphocyte culture supernatants was similar in 40 HIV-1(+) individuals and 35 HIV-1(-) controls. Our data show that plasma levels of IL-6 are significantly increased in HIV-1-infected individuals, in particular in ARC/AIDS patients. However, such an increase does not strictly correlate with the degree of hypergammaglobulinemia in the same HIV-1-infected individuals.