Fusidic acid is used in many countries for the treatment of multiresistant staphylococcal infection, especially multiresistant Staphylococcus aureus infection (MRSA). We collected consecutive fusidic acid-resistant isolates of staphylococci from the routine laboratory over several years, and compared these strains with fusidic acid-susceptible staphylococci to establish interpretive criteria for disk diffusion testing by National Committee for Clinical Laboratory Standards (NCCLS) methods. The minimum inhibitory concentrations (MICs) and zone diameters for strains of S. aureus (n = 102), including MRSA, S. saprophyticus (n = 20) and other coagulase-negative staphylococci (n = 115) were determined by NCCLS agar dilution and disk diffusion tests using a 2.5-micrograms disk of fusidic acid. MICs were bimodally distributed. No isolates had MICs of 0.5 or 1 microgram/ml; thus, we chose these values to define strains of intermediate susceptibility. The error-rate-bounded method was used to determine interpretive zone diameters for disk testing. Interpretive zone diameter criteria were found to be: susceptible > or = 22 mm, intermediate 18-21 mm, and resistant < or = 17 mm. All S. saprophyticus were intrinsically resistant to fusidic acid (MIC > or = 2 micrograms/ml).