Published reports have demonstrated that antigens of Mycobacterium avium complex (MAC) can suppress the normal response to mitogens in lymphoproliferation assays. We therefore studied the lymphoproliferative (LP) function of PBMC from 55 HIV-infected patients and 16 controls in response to mitogens with and without MAC antigen. As expected, LP responses decline with progressive decline in CD4 count; MAC antigen in combination with PHA further suppresses that response in a dose-dependent manner. More relevant were the LP responses in those with CD4 counts less than 100. All patients with MAC disease had poor responses (stimulation index, SI < 10) to PHA or anti-CD3 with or without MAC antigen. Those who did not have nor subsequently developed MAC were both good (SI > 10) or poor responders (SI < 10). The suppressive effect of MAC on lymphocyte function may serve as a weak virulence factor which is only relevant in severely immunocompromised HIV patients.