A Streptococcus pneumoniae strain selected for resistance to ethidium bromide demonstrated enhanced energy-dependent: efflux, of this toxic dye. Both the ethidium resistance and the ethidium efflux could be inhibited by the plant alkaloid reserpine. The ethidium-selected cells demonstrated cross-resistance to the fluoroquinolones norfloxacin and ciprofloxacin; this resistance could also be completely reversed by reserpine, Furthermore, reserpine potentiated the susceptibility of wild-type S, pneumoniae to fluoroquinolones and ethidium, The most plausible explanation for these results is that S, pneumoniae, like some other gram-positive bacteria, expresses a reserpine-sensitive multidrug transporter, which may play an important role in both intrinsic and acquired resistances of this pathogen to fluoroquinolone therapy.