The in vitro activity of the new naphthyridone trovafloxacin (CP 99,219) was compared with those of penicillin G and six other agents (cefpodoxime, erythromycin, azithromycin, clindamycin, ciprofloxacin, and sparfloxacin) against 316 penicillin-susceptible and -resistant pneumococci isolated in the former Czechoslovakia. Trovafloxacin was very active against strains of Streptococcus pneumoniae (MIC50 and MIC90 0.25 microgram/ml). Ciprofloxacin was less active (MIC50 1.0 microgram/ml, MIC90 2.0 micrograms/ml), and MICs of sparfloxacin were between those of trovafloxacin and ciprofloxacin (MIC50 and MIC90 both 0.5 microgram/ml). MICs of cefpodoxime, erythromycin, azithromycin, and clindamycin were higher for strains intermediately resistant or resistant to penicillin than for penicillin-susceptible strains.