Since the emergence of AIDS, disseminated Mycobacterium avium complex (MAC) infection has become a growing cause of morbidity and mortality in this group of patients. Our objective was to study the incidence and the clinical and microbiological features of MAC infection in HIV-positive patients as well as the response to a therapy regimen combining clarithromycin and ethambutol. At our hospital, the first patient with disseminated MAC infection was diagnosed in 1988. Since then, 54 HIV-positive patients with MAC infection have been diagnosed (30/1,000 HIV-positive patients). MAC represented 12% of recovered mycobacteria in HIV-positive patients and this percentage has increased from 3.9% in 1988 to 16.4% in 1994. All episodes of MAC infection occurred in patients with advanced HIV diseases (mean CD4: 73/microliter). MAC infection was the disease diagnosing AIDS in 23.4% of cases. The most common clinical manifestations included fever (85.7%), weight loss (55%), and pulmonary involvement (50%). A total of 55 specimens were processed for mycobacterial culture from 54 patients (mean of 10.2 specimens per patient). A total of 122 were positive (21.9%: 2.25 positive specimens per patient). The specimens with the greater percentage of positive results were bone marrow aspirates (65.3%) and blood cultures (47.7%), followed by respiratory (16.5%) and urine specimens (5.3%). Regarding therapy, sixteen of the 54 investigated patients did not receive specific drugs for MAC infection, 7 were treated with different combinations of active drugs against MAC (rifampin, clofazimine, amikacin, ethambutol, and isoniazid) and 31 received a combination of clarythromicin (1 g/12 hourly) and ethambutol (400 mg/12 hourly). Seventy-four percent of patients treated with clarythromicin and ethambutol improved clinically, and the mean survival time in these patients (253 days) was significantly longer than that in not treated patients (p < 0.05). No significant differences were noted in survival time between the group of patients treated with clarythromicin and ethambutol and that with other drug combinations. The incidence of disseminated MAC infection in our environment is increasing in patients with advanced HIV disease. The combination of clarythromicin plus ethambutol was well tolerated and efficient for the treatment of disseminated MAC infection.