Freshly isolated B lymphocytes from patients infected with human immunodeficiency virus (HIV), in contrast to B cells from normal controls, were shown to induce viral expression in two cell lines: ACH-2, a T cell line, and U1, a promonocytic cell line, which are chronically infected with HIV, as well as in autologous T cells. In 10 out of 10 HIV-infected individuals with hypergammaglobulinemia, spontaneous HIV-inductive capacity was found with highly purified peripheral blood B cells, whereas peripheral blood or tonsillar B cells from six healthy, HIV-negative donors did not induce HIV expression unless the cells were stimulated in vitro. The induction of HIV expression was observed in direct coculture experiments of B lymphocytes and HIV-infected cells, and could also be mediated by supernatants from cultures of B cells. Significantly higher amounts of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were detected in the B cell culture supernatants from HIV-infected patients with hypergammaglobulinemia (IL-6: mean = 536 pg/ml; TNF-alpha: mean = 493 pg/ml), as compared with normal uninfected controls (IL-6: mean = 18 pg/ml; TNF-alpha: mean = 23 pg/ml). Antibodies against these cytokines abolished the HIV-inductive capacity of B cells. We conclude that in vivo activated B cells in HIV-infected individuals can upregulate the expression of virus in infected cells by secreting cytokines such as TNF-alpha and IL-6, and, therefore, may play a role in the progression of HIV infection.