Patients with AIDS and disseminated Mycobacterium avium complex disease (DMAC), as defined by the presence of a positive blood culture for MAC, were studied retrospectively to define the natural history of DMAC. All patients had fevers, severe anemia (hematocrit <26%), or both. Eighty-seven (76%) had signs, symptoms, or laboratory findings related to the gastrointestinal tract, but no distinct syndrome was identified. Sixty-nine patients received antimycobacterial therapy; assignment to therapy was not randomized. In a proportional hazards analysis, shorter survival was associated with higher initial level of mycobacteremia (relative risk [RR], 1.86; 95% confidence interval [CI], 1.49-2.31; P < .001), while administration of antimycobacterial chemotherapy (RR, 0.42; 95% CI, 0.26-0.70; P < .001) and antiretroviral therapy (RR, 0.40; 95% CI, 0.22-0.73; P < .01) had protective effects. Thus, the initial level of mycobacteremia of patients with DMAC may have prognostic value, and administration of antimycobacterial and antiretroviral agents may be associated with prolonged survival.