This study assessed the regulatory role of peripheral blood T cells in the C3 production in patients with poststreptococcal glomerulonephritis and membranoproliferative glomerulonephritis. Peripheral blood T cells from patients at various stages of disease were cultured and the supernatants tested for gamma interferon (IFN-γ) content and the capacity to stimulate C3 production by HuH-7 cells. Supernatants from patients with membranoproliferative glomerulonephritis and from convalescent patients with poststreptococcal glomerulonephritis significantly stimulated the C3 production; the degree of stimulation correlated with the IFN-γ content of the supernatants. Similar results were obtained using recombinant IFN-γ. In both cases, the effect was blocked by the addition of anti-IFN-γ monoclonal antibody to the cultures. Interleukin 2 and interleukin 6 levels in supernatants from T cell cultures of patients and controls were essentially the same. In summary, IFN-γ plays a regulatory role in C3 production by human hepatoma cell lines.