Interleukin-10 (IL-10) has been shown to down-regulate a number of different macrophage functions, including microbicidal activity against intracellular bacteria or parasites. In this study, peripheral blood mononuclear cells (PBMC) obtained from a healthy tuberculin-reactor were stimulated in vitro with various strains of multidrug-resistant Mycobacterium tuberculosis (MDRTB) or drug-sensitive M. tuberculosis (DSTB) to produce IL-10. We obtained one mycobacterial strain from each patient, preparing a total of 10 strains of DSTB, 5 strains of MDRTB. PBMC were cultured with LPS or mycobacterial preparations for 1, 3 and 5 days. IL-10 concentration in the culture supernatants was measured by ELISA using IL-10-specific monoclonal antibodies. The mean IL-10 production by PBMC stimulated with MDRTB was greater than that with DSTB, statistically significant at day 3 (MDRTB 171.4 +/- 18.2 pg/ml, DSTB 106.3 +/- 17.2 pg/ml, p < 0.05). Cell separation experiments indicated that cells producing IL-10 when stimulated with M. tuberculosis or LPS were monocytes, not T lymphocytes. Next, we examined PBMC from refractory tuberculosis patient who had continuously excreted MDRTB. PBMC from those patients secreted greater, but statistically not significant, amounts of IL-10 in response to LPS or TB bacilli than those of healthy subjects. Increased production of IL-10 by MDRTB-stimulated PBMC might be responsible for intractable tuberculosis.