In a context of worldwide emergence of resistance among Streptococcus pneumoniae strains, early detection of strains with decreased susceptibility to -lactam antibiotics is important for clinicians. If the 1-µg oxacillin disk diffusion test is used as described by the National Committee for Clinical Laboratory Standards, no interpretation is available for strains showing zone sizes of 19 mm, and there is presently no disk diffusion test available for screening cephalosporin resistance. The zones obtained by the diffusion method by using the 1-µg oxacillin disk were compared with penicillin MICs for 1,116 clinical strains and with ceftriaxone MICs for 695 of these strains. Among the 342 strains with growth up to the 1-µg oxacillin disk margin, none were susceptible (MIC, 0.06 µg/ml), 62 had intermediate resistance (MIC, 0.12 to 1.0 µg/ml), and 280 were resistant (MIC, 2.0 µg/ml) to penicillin. For ceftriaxone, among 98 strains with no zone of inhibition in response to oxacillin, 68 had intermediate resistance (MIC, 1.0 µg/ml), and 22 were resistant (MIC, 2.0 µg/ml). To optimize the use of the disk diffusion method, we propose that the absence of a zone of inhibition around the 1-µg oxacillin disk be regarded as an indicator of nonsusceptibility to penicillin and ceftriaxone and recommend that such strains be reported as nonsusceptible to these antimicrobial agents, pending the results of a MIC quantitation method.