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The drug susceptibility of two untypable strains of Mycobacterium avium complex were studied in 7H10 agar plates containing ethambutol (EMB), isoniazid (INH), rifampicin (RMP), ethionamide (ETH), and streptomycin (SM) alone and in two-drug combinations. The effective dose inhibiting 75% of the mycobacterial population (ED 75) was estimated by a regression analysis on the probit transformed inhibition percentages and plotted on an isobologram for each combination. No major discrepancies were found between strains. Five combinations (RMP plus INH, RMP plus EMB, EMB plus SM, INH plus EMB, and ETH plus INH) showed synergistic effect, whereas five other combinations (ETH plus EMB, ETH plus RMP, ETH plus SM, SM plus RMP, and SM plus INH) showed antagonistic effect. These in vitro results are not in combination with the known results of treatment of the M. avium diseases. We conclude that the effect of drug combinations against M. avium may be strain dependent and that it is important to determine this effect in vitro before setting up a treatment protocol.