From January 1986 through February 1993, there were 16 episodes of respiratory infection due to Corynebacterium pseudodiphtheriticum in 13 patients. The ages of patients ranged from 24 to 77 years; the ratio of male to female patients was 3:1. One patient had three episodes of infection, and another patient had two. In one patient, who died of disseminated intravascular coagulation, the level of IgG was low. One patient was receiving prednisolone when the infection occurred. In two cases a mixed infection with Streptococcus pneumoniae was noted. Sputum cultures yielded C. pseudodiphtheriticum (> or = 10(7) cfu/mL). An increased neutrophil response in the sputum of infected patients was observed. Gram staining and electron microscopy of sputum showed phagocytosis of C. pseudodiphtheriticum by the neutrophils. ELISAs also showed an increase in the level of immunoglobulin against C. pseudodiphtheriticum after infection. Tests for determination of MICs of antibiotics revealed that C. pseudodiphtheriticum isolates were susceptible to ampicillin, amoxycillin/clavulanic acid, cefazolin, cefuroxime, ceftazidime, and imipenem. All strains were resistant to nalidixic acid; borderline susceptibility to ofloxacin, norfloxacin, and ciprofloxacin was noted. We suggest the use of beta-lactam antibiotics in the treatment of infection with C. pseudodiphtheriticum.