Using reverse transcription-polymerase chain reaction (RT-PCR) technique, the messenger RNA (mRNA) for tumor necrosis factor receptor type 2 (TNF-R2, 75/80 kDa) was detected in rat primary astrocytes, with much lower level of expression when compared to that for tumor necrosis factor receptor type 1 (TNF-R1, 55/60 kDa). Upon exposure to TNF-alpha (100 U/ml), the TNF-R2 mRNA level was greatly enhanced at 8 h, while TNF-R1 mRNA remained unchanged even after 24 h. The induction of TNF-R2 gene expression by TNF-alpha was dose-dependent and seemed to be unique to TNF-alpha, as interleukin-6 (IL-6) had no significant effect on TNF-R2 expression. Since TNF-R2 was reported to mediate mitogenic and gene-inducing effects in many other cell types, it is likely that the reported proliferative effect of TNF-alpha on astrocytes was also mediated by this TNF receptor subtype. Upon exposure to TNF-alpha or lipopolysaccharide (LPS), the expression of TNF-alpha gene was induced, and the LPS-induced TNF-alpha seemed to selectively enhance the TNF-R2 gene expression. Collectively, our results suggest that the TNF-alpha or LPS-induced expression of both TNF-R2 and TNF-alpha may provide a positive control mechanism to further enhance the proliferative effect of TNF-alpha in astrocytes.