Disturbance of T cell-mediated immunity has been reported in acute visceral leishmaniasis (AVL). In a study of 16 patients with AVL, defective production of interleukin-1 (IL-1) by peripheral blood mononuclear cells was demonstrated in response to leishmania antigens, heat-killed Listeria organisms, and lipopolysaccharide when compared to posttherapy values or controls. This global defect in IL-1 production was corrected after successful therapy. Twelve of 16 patients responded with a greater than or equal to 2.5-fold increase in IL-1 production that correlated with clinical cure, P less than .01. Depressed production of tumor necrosis factor (TNF) was leishmania antigen-specific and similarly recovered after therapy. In vitro TNF production during the follow-up period did not correlate with clinical status but high serum levels were associated with AVL. Since T cells are activated by processed antigens presented on class II major histocompatibility molecules and by newly synthesized IL-1, defective IL-1 production may contribute to the immunosuppression observed in AVL.