Clarithromycin and rifabutin are among the most promising drugs for the therapy of infections caused by Mycobacterium avium or other atypical mycobacteria. Since synergism of combined drugs is important in order to achieve strong antimycobacterial activity, the combined inhibitory effects of antibacterial agents should also be investigated when agents are evaluated for possible use in antimycobacterial drug therapy. In the present study we examined the antimycobacterial activity of clarithromycin, rifabutin, and their combination against 51 clinical isolates of the M. avium complex from patients with acquired immune deficiency syndrome (AIDS) with disseminated mycobacteriosis. A concentration-dependent inhibition was seen for each drug. The antibacterial effect was significantly more pronounced for the combined drugs than for the agents tested separately. Synergism, against up to 88% of the strains tested, was seen for the tested drugs combined at different concentrations. All 51 M. avium strains were susceptible to the combination of 4 mg/l clarithromycin and 2 mg/l rifabutin.