A smear of the buffy coat of peripheral blood for acid-fast bacilli was assessed for sensitivity and specificity in the diagnosis of disseminated Mycobacterium avium complex (MAC) infection in acquired immunodeficiency syndrome (AIDS) patients. Seventeen AIDS patients with blood cultures positive for MAC had simultaneous quantitative blood cultures and buffy coat smears performed, as did 4 patients later proven not to have disseminated MAC. The sensitivity of the buffy coat smear for the detection of MAC was 35%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 22%. We conclude that the buffy coat smear is a rapid, simple, and specific method of diagnosis of disseminated MAC infection in AIDS patients, although it is not very sensitive.