Coumermycin was found to be extremely active against methicillin-susceptible and -resistant Staphylococcus spp. (MIC 90, less than or equal to 0.002 microgram/ml). Vancomycin and coumermycin were equally active against Streptococcus spp. (MIC 90s, 0.5 microgram/ml) and both were superior to fusidic acid (MIC 90, 8.0 micrograms/ml). The enterococci had the highest MICs for all three drugs. Disk diffusion susceptibility tests using either 5 or 15 micrograms coumermycin disks seem reliable. The tentative interpretive breakpoints for testing the Staphylococcus spp. only are: 5 micrograms disk-susceptible greater than or equal to 17 and resistant less than or equal to 13 mm; 15 micrograms disk-susceptible greater than or equal to 20 mm and resistant less than or equal to 16 mm. These zone criteria have approximate coumermycin MIC correlates of less than or equal to 0.12 microgram/ml for susceptible and greater than or equal to 0.5 microgram/ml for resistant.