The pharmacokinetic interaction between phenytoin and ciprofloxacin was studied in rats. One group of animals was given phenytoin (20 mg/kg, p.o.) as a single daily dose for 7 days. In another group of animals, the same protocol was followed except that ciprofloxacin was given in two equal doses (15 mg/kg, i.p., each) on days 5, 6 and 7. On day 8, phenytoin blood sampling was performed at 0.083, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0 and 12.0 h. Similarly, urine samples were collected at 4, 6 and 8 h following drug administration from the same animals that had received either phenytoin alone or phenytoin together with ciprofloxacin. The concentrations of phenytoin in the plasma and urine were measured using an HPLC method. Ciprofloxacin significantly (P < 0.05) reduced the area under the curve (AUC), the maximum plasma concentration (Cmax) and the elimination half-life (t1/2) of phenytoin. Additionally, ciprofloxacin increased phenytoin concentrations in urine at 4, 6 and 8 h. These results show that ciprofloxacin decreases the plasma levels of phenytoin when the two drugs are given concurrently.