The in vitro effect of clindamycin on the inhibitory and bactericidal activity of amikacin (BB-K8) and gentamicin against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa was examined by the checkerboard technique in microtiter plates. Clindamycin (15 mug/ml) produced statistically significant increases in the minimal bactericidal concentrations of amikacin and gentamicin against E. coli and Klebsiellae at 2 and 4 h of incubation. The minimal bactericidal concentration against P. aeruginosa was not affected. Higher concentrations of clindamycin (20 to 25 mug/ml) reduced the minimal inhibitory and bactericidal concentrations of amikacin and gentamicin for E. coli at 18 h of incubation. The synergistic bactericidal activity of amikacin and carbenicillin against E. coli, but not P. aeruginosa, was also inhibited slightly by clindamycin (15 mug/ml). The clinical implications of this inhibition of the early bactericidal in vitro activity of aminoglycosides by clindamycin remain to be determined. Although these in vitro results have not been studied in clinical infections, it is conceivable that slight interference in early bacterial killing could alter the outcome of infection in the immunosuppressed patient.