The effect of ampicillin and sulbactam on the interaction in vitro of human polymorphonuclear leukocytes (PMN) with Staphylococcus aureus was examined. The exposure of a non-penicillinase-producing S. aureus strain to one fourth the MIC of ampicillin but not of sulbactam significantly increased the uptake of bacteria by human PMN. This effect was also observed when bacteria were exposed to the MIC0.25 of different combinations of ampicillin and sulbactam (2/1, 1/1, 1/4, 1/8 and 1/32). These effects were not observed when a penicillinase-producing strain was used. The production of superoxide and hydrogen peroxide radicals by human PMN was not affected by the presence of these antimicrobials. Ampicillin and sulbactam, neither alone nor in combination, showed intracellular activity against S. aureus within human PMN.