To determine whether counterregulation by interleukin (IL)-10 plays a role in the generation or maintenance of the antigen-specific hyporesponsiveness seen in asymptomatic microfilaremic (MF) patients, parasite antigen (PAg)- and nonparasite antigen (NPAg)-driven IL-10 production by peripheral blood mononuclear cells (PBMC) was studied in 10 MF patients and in 11 patients with chronic lymphatic pathology (CP). PBMC from MF patients spontaneously secreted ~10-fold more IL-10 than did PBMC from patients with CP. PAg also induced significantly more IL-10 production by PBMC from MF than from CP patients. There was a negative correlation between PAg-driven IL-10 production by PBMC and PAg-specific T cell proliferation in the MF group. IL- 10 secretion by plastic adherent cells from MF persons was higher in response to PAg than to NPAg, whereas IL-6 and tumor necrosis factor-α secretion were equivalent for PAg and NPAg, suggesting that PAg preferentially induces IL- 10 secretion in these cells. Thus, PAg-induced IL-10 likely plays an important role in down-regulating antigen-specific proliferative responses in MF patients.