To determine the incidence and natural history of Mycobacterium avium-complex infections in persons with advanced human immunodeficiency virus (HIV) infection, we studied a multicenter cohort of 1,020 persons with acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex (ARC) and CD4 cell count < 0.250 x 10(9)/L initially treated with zidovudine between April 1987 and April 1988. M. avium-complex infections developed in 123 (12%) patients during follow-up, with a 2-yr actuarial risk of 19%. Patients with an initial diagnosis of Pneumocystis carinii pneumonia were more likely to develop M. avium-complex infections than patients with an initial diagnosis of another opportunistic disease or of ARC (p = 0.002). Individuals developing M. avium-complex infections had lower baseline CD4 cell counts, hematocrits, lymphocyte counts, and total white blood cell counts than those who did not develop M. avium-complex infection. During follow-up, individuals who developed M. avium-complex infections were more likely to have severe anemia, to experience zidovudine dose reductions, and to die than were patients without M. avium-complex (p < 0.001). By proportional hazards analysis, a baseline CD4 cell count < 0.100 x 10(9)/L, development of severe anemia, P. carinii pneumonia during follow-up, and zidovudine dose interruption were significantly associated with subsequently developing M. avium-complex infection. A proportional hazards analysis of survival showed that M. avium-complex infection, severe anemia, zidovudine dose interruption, occurrence of an opportunistic infection, CD4 cell count < 0.100 x 10(9)/L, baseline AIDS diagnosis, and transfusion independently predicted an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)