Mycobacterium avium-intracellulare complex (MAC) consists of 28 serotypes. Co-infection of several specific serotype strains with the advent of acquired immunodeficiency syndrome (AIDS) has been dramatically increasing in the past fifteen years, although the reason for this fact is not clearly understood. Since the cell surface lipid components of MAC impaired the capacity of human peripheral blood mononuclear cells (PBMC) to proliferate, some particular glycopeptidolipid (GPL) with serologically specific carbohydrate chains are supposed to inhibit blastogenesis and to affect the immune response in MAC infection. In this study, we have investigated the effect of serovar 4 and 16 GPLs on the human PBMC function and cell mediated immunity. As the result, it was demonstrated that the percentage of viable cells was decreased prominently after the incubation of PBMC with the serovar 4 GPL. Blastogenic responses of PBMC to stimulation with the purified protein derivatives (PPD) were inhibited by the presence of GPL dose-dependently. In the case of stimulation with anti-CD3 antibody (a-CD3 Ab), blastogenic response of PBMC was suppressed markedly by GPL at the concentration of 175 micrograms/ml. Flow-cytometric analysis demonstrated that the expression of interleukin-2 receptor alpha on a-CD3 Ab-stimulated T lymphocyte was markedly inhibited in the presence of GPL. Enzyme-linked immunosorbent assay showed that the production of interleukin-2 by a-CD3 Ab-stimulated PBMC was reduced dose-dependently after the incubation of PBMC with GPL. In these results, there was no remarkable difference between serovar 4 and serovar 16 GPLs. These results indicate that serovar 4 and 16 GPLs inhibit the cell mediated immunity and serovar 4 GPL can affect the viability of PBMC.