The coccidian Toxoplasma gondiiis an obligate intracellular parasite which can infect all cell types. Among the cytokines elicited by the immune response to Toxoplasma, tumor necrosis factor alpha (TNF-alpha) acts synergistically with gamma interferon (IFN-gamma) and plays a major role in host cell resistance. We have previously reported that TNF-alpha production induced by IFN-gamma/LPS decreases after T. gondii infection of human myelomonocytic THP-1 cells. Here, we investigated the regulation of TNF-alpha and its specific receptors during T. gondii infection of THP-1 cells. We found that TNF-alpha production was regulated at a post-transcriptional level and that TNF receptor expression was regulated at a pretranscriptional level. The TNF receptor I shedding and the fall in TNF-alpha levels observed after T. gondii infection would thus be induced by a parasite component with serine protease activity. These findings indicate that T. gondii participates not only in controlling the cytotoxic effects of TNF-alpha during the infection process, but also in signal transduction mediated mainly by TNF receptor I.