This report examines the effects of exposure to enoxacin on interactions of bacteria and neutrophils. Pretreatment of Streptococcus pneumoniae and Pseudomonas aeruginosa with x 1/2 to x4 the MIC of enoxacin had no enhancing effect upon phagocytic killing when the antibiotic was not present. Phagocytic killing was synergistically enhanced when enoxacin was continually present although this was not manifested in increased phagocytosis. The enhanced killing was abrogated by disruption of bacterial opsonization, internalization and intraleukocytic killing processes of polymorphonuclear leukocytes. These observations indicate that the synergistic killing of Str. pneumoniae and Ps. aeruginosa by enoxacin and human neutrophils is due to enhanced intracellular killing and not an increase in phagocytosis.