Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents, Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro antipneumococcal activity might be particularly useful against strains that are resistant to the more traditional therapeutic agents.