Neither amoxicillin nor clavulanic acid used alone was active at the highest level tested, i.e., 256.0 mu g/ml, in vitro against 24 isolates of Mycobacterium fortuitum, Mycobacterium kansasii, and Mycobacterium marinum, However, the MIC of an amoxicillin-clavulanic acid combination of 2:1 was less than or equal to 8.0/4.0 mu g/ml for 50 percent of the isolates tested, with all isolates being inhibited in the range of 4.0/2.0 to 32.0/16.0 mu g/ml, respectively, Titration of amoxicillin-clavulanic acid with a fixed 2-mu g/ml concentration of ethambutol resulted in synergistic activity against 3 of 9 isolates of M. fortuitum, 10 of 10 isolates of M. kansnsii, and 5 of 5 isolates of M. marinum, This observation was confirmed in a checkerboard analysis in which fractional inhibitory concentrations were less than or equal to 0.5 for 20 of the 24 isolates, Synergistic activity was observed against the other four isolates in one of two trials, On the other hand, titration of amoxicillin-clavulanic acid in the presence of either one or two fixed concentrations of isoniazid, rifampin, cycloserine, tetracycline, or amikacin failed to result in synergism.