The effects of ofloxacin in Salmonella typhimurium infection in mice were compared with those of ciprofloxacin, ampicillin and chloramphenicol. Oral administration of ofloxacin at 10, 50 or 100 mg/kg once per day for seven days significantly (P < 0·02) increased survival (20·1 days at 100 mg/kg) of infected mice relative to non-treated controls (4·1 days). In addition, after oral treatment with 100 mg/kg of each of the antibiotics, ofloxacin was significantly more effective than ampicillin (9·9 days), chloramphenicol (8·4 days) or ciprofloxacin (14·9 days) in prolonging the mean survival time of these mice. A comparison of oral potencies indicates that ofloxacin is five times more potent than ciprofloxacin (oral ED50 =13·3 mg/kg vs ciprofloxacin = 69·9 mg/kg) and over eight times more potent than either of the other two antibiotics. When the number of bacteria from livers and spleens was quantitated, only ofloxacin (25 or 100 mg/kg, po) significantly (P < 0·02) reduced the number of viable bacteria in both of these tissues in comparison with untreated controls, and, relative to the other antibiotics, ofloxacin (100 mg/kg) caused a significantly greater reduction. Single oral dosing of 20 mg/kg of either ofloxacin or ciprofloxacin showed that ofloxacin achieves approximately a four-fold higher peak serum or liver concentration than ciprofloxacin, which may contribute to its better efficacy in this infection model. These results taken together suggest that oral ofloxacin may be of value in treating systemic salmonella infections in humans.