Cellular host defenses are considered to be ineffective in bacterial endocarditis; the microorganisms in infected vegetations are protected from phagocytic cells by dense layers of fibrin. To test this hypothesis, nitrogen mustard-induced agranulocytosis and leukopenia were produced in rabbits with right-sided streptococcal endocarditis. The spontaneous sterilization of tricuspid infection observed in the control animals was not present in the granulocytopenic, leukopenic animals. Since the bacterium Streptococcus intermedius is not sensitive to the complement-mediated bactericidal effect of serum and since the animals were not bacteremic during the time of agranulocytosis, an inhibitory effect of the drug on local cellular host defense mechanisms is postulated. We suggest that the spontaneous sterilization of infective endocarditis in the right side of the heart in rabbits is mediated by cellular host defenses.