The reliabilities of five in vitro susceptibility tests (agar dilution, broth microdilution, automated MS-2, Kirby-Bauer disk diffusion, and ability to grow on methicillin-containing agar) to predict the susceptibility of 204 coagulase-negative staphylococcal isolates to penicillinase-resistant semisynthetic penicillins were compared. There was wide variation in susceptibility, with results ranging from 86.3% susceptible by MS-2 to 38.2% by growth on methicillin-containing agar. The results of the broth dilution techniques, including the MS-2, were significantly different (P less than 0.02) from the remaining tests. Nafcillin disks were less effective (P less than 0.02) than oxacillin disks in predicting resistance. Kirby-Bauer oxacillin disks and the ability to grow on methicillin-containing agar were the most reliable predictors of resistance. The MS-2 did not reliably predict resistance.