MICs of six oral cephalosporins (cefdinir, cefpodoxime, cefaclor, cefuroxime, cefixime and Ro 40-6890), four quinolones (ciprofloxacin, ofloxacin, OPC-17116 and fleroxacin), desacetylcefotaxime, Ro 23-9424 (a fused combination of fleroxacin + desacetylcefotaxime) and RP 67829 (a benzonaphthyridine) were determined for 49 penicillin-susceptible (S), 38 penicillin-intermediate (I), and 83 penicillin-resistant (R) strains of Streptococcus pneumoniae. All MICs were determined by a standardized agar dilution method utilizing Mueller-Hinton agar supplemented with sheep blood. MIC90s of OPC-17116 and RP 67829 were < or = mg/L, and were unaffected by penicillin-susceptibility. MICs of all beta-lactams increased with increasing penicillin-MICs, with cefdinir, cefpodoxime, cefuroxime and Ro 40-6890 being the most active compounds, followed by cefaclor and cefixime. MIC90s of ciprofloxacin and ofloxacin were 2 mg/L. MIC90s of Ro 23-9424 were lower than those of either parent compound (fleroxacin 8 mg/mL for all three groups; desacetylcefotaxime 0.5 mg/mL [S], 0.5 mg/mL [I], 4 mg/mL [R]; Ro 23-9424 0.125 mg/L [S], 0.25 mg/L [I], 0.5 mg/L [R]). The results indicated that several newly introduced and experimental antimicrobials have potential for the treatment of infections caused by resistant strains of S. pneumoniae.