The in vitro activity of S-565, a semi-synthetic rifamycin chemically related to rifampicin but with a longer half-life, has been compared with that of rifampicin, ciprofloxacin, spectinomycin, azithromycin and amoxycillin against Neisseria gonorrhoeae. Modal MICs against 20 strains were 0.13 mg/l for rifampicin and 0.5 mg/l for S-565. There was cross-resistance between the two rifamycins, and each selected for resistance at similar rates. In a time-kill study, S-565 was more rapidly bactericidal than rifampicin at 1 and 2 MIC.