For the first time, the effects of combinations of trimethoprim and a fluoroquinolone (ciprofloxacin) against gram-positive and gram-negative bacterial isolates were evaluated in vitro. Synergism was found in 31 % (fractional inhibitory concentration, FIC) and 33 % (fractional bactericidal concentration, FBC) of 121 clinical isolates of various bacterial strains, most often in Escherichia coli, staphylococci, and enterococci. Antagonism occurred in 1 % (FIC) and 3 % (FBC). The combination of trimethoprim and ciprofloxacin merits further evaluation for potential usefulness as a clinical regimen.