The susceptibility of 10 multiply antibiotic-resistant strains of Streptococcus pneumoniae to several quinoline antibiotics and to coumermycin, novobiocin, and penicillin was determined. The MIC of penicillin for all test isolates was greater than or equal to 4 micrograms/ml. Ciprofloxacin was the most active quinoline derivative tested, followed by norfloxacin. These isolates of S. pneumoniae were not inhibited by the remaining quinolines at achievable concentrations in serum. Coumermycin and ciprofloxacin were the most active antibiotics tested in this study.