• During the three-year period from 1981 to 1984, all clinical isolates of Streptococcus pneumoniae were screened for resistance to penicillin in the clinical bacteriology laboratory at The Children's Hospital of Alabama, Birmingham. Twenty-eight of 828 isolates were presumed resistant by disk diffusion testing with 1-μg oxacillin disks (zone diameter, 20 mm). Seventeen of the 28 (61%) were found to be intermediately sensitive to penicillin by a conventional agar dilution method. Penicillin-intermediate strains had a minimal inhibitory concentration of 0.125 to 0.5 mg/L; no penicillin-resistant (minimal inhibitory concentration, >1 mg/L) strains were encountered. The prevalence of penicillin-intermediate strains was thus 17 of 828 isolates, or 2.1%. These strains were also examined for susceptibility to ampicillin, vancomycin, cefotaxime, and chloramphenicol. We present the clinical features of 17 patients with disease due to penicillin-intermediate pneumococci.