MICs of clarithromycin against 324 clinical isolates belonging to eight species of slowly growing nontuberculous mycobacteria were determined by using a broth microdilution system. Isolates were inoculated into twofold drug dilutions in Middlebrook 7H9 broth (pH corrected to 7.4) and then incubated at 30 degrees C for 7 days for Mycobacterium marinum and for 14 days for all other species. The MIC for 90% of the strains (MIC90) was less than or equal to 0.5 micrograms/ml for isolates of Mycobacterium gordonae (6 strains), Mycobacterium scrofulaceum (5 strains), Mycobacterium szulgai (6 strains), and Mycobacterium kansasii (35 strains). MICs for M. marinum (25 strains) and Mycobacterium avium complex (237 strains) were higher, but 100% and 89% of the strains, respectively, were susceptible to less than or equal to 4 micrograms/ml. In contrast, MICs for five of six M. simiae strains were greater than 8 micrograms/ml, and the range of MICs for Mycobacterium nonchromogenicum varied from less than or equal to 0.125 to 8 micrograms/ml. For the 237 isolates of M. avium complex, the MIC50 was 2 micrograms/ml and the MIC90 was 8 micrograms/ml. MICs for most isolates (77%) were in the 1- to 4-micrograms/ml range. For the 80 isolates in this group known to be from AIDS patients, the MIC50 was 4 micrograms/ml and the MIC90 was 8 micrograms/ml. These MIC studies combined with preliminary clinical trials suggest that clarithromycin may be useful for drug therapy of most species of the slowly growing nontuberculous mycobacteria except M. simiae.