Nerve growth factor (NGF) may mediate responses to brain injury. To examine regulation of NGF gene expression with respect to neural trauma we examined the effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) on NGF production in cultures of rat astroglial cells. Purified neocortical astrocytes in serum-free medium were treated with IL-1 beta, TNF-alpha or both. Whereas IL-1 beta and TNF-alpha alone elicited only small effects, simultaneous addition elicited within 48 h a large (3- to 6-fold) increase in NGF content in culture supernatants. Our data are consistent with a role for cytokines in NGF synthesis and release in the injured central nervous system (CNS).