After exposure to erythromycin, group A streptococci were tested for susceptibility to the antimicrobial activity of human peripheral blood neutrophils in the absence of the antibiotic. Bacterial susceptibility to phagocytic killing increased after prior exposure to suprainhibitory levels of erythromycin for even as brief as three minutes. Extended exposure and higher concentrations of erythromycin increased phagocytic killing. Although the degree of sensitization varied in different strains of streptococci, all strains tested were significantly more susceptible to phagocytic killing after erythromycin exposure. Killing of erythromycin-treated bacteria that occurred in the absence of antibiotic was dependent upon internalization of the bacteria. Thus, the brief exposure of group A streptococci to inhibitory levels of erythromycin increases their susceptibility to phagocytic killing by peripheral blood neutrophils.