As a reflection of the close relationship between their causative organisms, actinomycosis and nocardiosis present considerable over-all similarity, although possessing too many basic differences to be regarded as other than two separate and distinct diseases. Both are caused by branching, fragmenting, filamentous fungi, Actinomyces bovis being fastidious and growing only at incubator temperature under anaerobic or microaerophilic conditions, while Nocardia asteroides flourishes on all common laboratory media at both room and incubator temperatures. Both organisms are gram-positive, but N. asteroides is acid-fast whereas A. bovis is not. A. bovis exhibits little pathogenicity for laboratory animals; N. asteroides is typically quite lethal, yet either can reside as a saprophyte within the human tracheobronchial tree and elsewhere. The natural habitat of A. bovis is the human mouth and oropharynx, while that of N. asteroides is the soil. Hence actinomycosis is considered endogenous, and nocardiosis exogenous, in origin. Actinomycosis is fairly common; nocardiosis, perhaps unjustly so, is looked upon as rare. Each has a world-wide distribution. Clinically the two diseases may be indistinguishable, with chronic pleuro-pulmonary lesions, subcutaneous abscesses, and multiple draining sinuses typifying both. Any organ may be involved, but hematogenous dissemination is not only more common but almost characteristic of nocardiosis, with the combination of lung and brain involvment being quite outstanding. Histologically there is nothing to separate the two diseases, although actinomycotic granules (sulfur granules) are more characteristic of actinomycosis than nocardiosis. In each disease the basic lesion is more suppurative than granulomatous. Because of the tendency of both organisms to fragment into bacillary forms either may be mistaken for bacteria, with further confusion resulting from the acid-fastness of N. asteroides. Perhaps the sharpest practical distinction between the two diseases is in the matter of therapy. A. bovis is quite sensitive to penicillin, which is the drug of choice in actinomycosis, and to a lesser extent also to sulfadiazine and the broad-spectrum antibiotics. N. asteroides, on the other hand, is resistant to penicillin, and the drug of choice is sulfadiazine. In view of the extreme seriousness of most nocardial infections sulfadiazine is probably best given in combination with streptomycin or whatever broad-spectrum antibiotic appears most effective in vitro. In both diseases, but especially in nocardiosis, treatment must be instituted early if cure is to be effected and must be continued in high dosage for prolonged periods if relapse is to be prevented.