Cefotaxime, a cephalosporin drug, has been shown to be active in vitro against nocardiae, a finding confirmed in this study. Pharmacokinetic studies were performed in mice to define regimens which provided peak serum levels comparable to that achieved in man with currently used doses. These regimens were shown to be effective with only short courses of therapy of rapidly progressive and highly lethal N. asteroides infection, produced by pulmonary challenge of mice. This suggests the possible utility of this drug in human nocardiosis.