The capacity of two human fetal glial cell lines, SVG and POJ, to increase the expression of human immunodeficiency virus (HIV) was investigated. As a cellular model for HIV latency, a chronically infected promonocytic cell line U1 was used. This cell line constitutively expresses a low level of viral activity. To monitor the level of HIV expression in U1 cells, reverse transcriptase (RT) activity was measured in the supernatant and the level of total HIV proteins was determined in cellular lysates. It was observed that the conditioned media from SVG and POJ cells increased RT activity in U1 cells in a dose-dependent fashion. In addition, the conditioned media from fetal glial cells caused an increase in total HIV protein synthesis. The capacity of conditioned media from both fetal glial cell lines to induce the expression of HIV was reduced by 45% in the presence of antibodies against human tumor necrosis factor alpha (TNFalpha), suggesting that one of the HIV-activating factors released by these cells was TNFalpha. The presence of TNFalpha and two other HIV-activating cytokines, IL-6 and IL-1, was confirmed by ELISA. It was also observed that glutathione increased the HIV-inducing capacity of the fetal glial cell-derived conditioned media. The finding that fetal glial cells constitutively secrete soluble factors which increase the expression of HIV in vitro suggests that in vivo, during perinatally acquired infection, similar events may occur. Fetal glial cells may play an important role in the pathogenesis of HIV-related encephalopathy.