Intracellular bactericidal activity of ampicillin/sulbactam and erythromycin was determined with a human macrophage-like (U-937) cell line infected with Legionella pneumophila. Cell monolayers inoculated with L. pneumophila were treated with erythromycin, ampicillin, sulbactam, or ampicillin/sulbactam during the logarithmic phase of bacterial growth. Intracellular bacterial counts were determined at 2-h intervals for 8 h from the time that antibiotics were added. The number of viable intracellular bacteria increased during this time by 0.9 x log10 cfu/mL (P < 0.05) in the control culture, did not change significantly in the cultures treated with ampicillin or sulbactam, decreased by 0.8 x log10 cfu/mL (P < 0.05) with erythromycin, and decreased by 1.8 x log10 cfu/mL with ampicillin/sulbactam (P < 0.05). The number of cfu/mL was significantly less after incubation with ampicillin/sulbactam than with erythromycin (P < 0.05). Ampicillin/sulbactam appeared to have greater bactericidal activity against intracellular L. pneumophila than erythromycin in this in-vitro model. The bactericidal action of ampicillin/sulbactam was significantly greater than would be expected from the additive effects of ampicillin plus sulbactam, suggesting synergic bactericidal activity.