The potential pharmacokinetic interaction between atovaquone and phenytoin was investigated in 12 healthy male volunteers. Each volunteer received a single 600 mg oral dose of phenytoin in the two treatment periods. On one occasion phenytoin was taken alone and on the other pre-treatment with 2000 mg atovaquone taken as two doses of 1000 mg as a microfluidized suspension. The mean (+/- s.d.) peak plasma concentrations (Cmax), apparent total clearance (CL/F) and terminal half-life (t1/2) for phenytoin when administered alone were 10.6(1.8) mg 1(-1), 24.3 (7.7) ml min-1 and 25(8) h, respectively. When administered together with atovaquone, phenytoin Cmax, CL/F and t1/2,z were 10.9 (2.0) mg 1(-1), 23.8 ml min-1 and 24(6) h, respectively. There were no statistically significant differences in any of these plasma pharmacokinetic parameters. There were also no statistically significant differences in the fraction of circulating drug not bound to plasma protein or urinary excretion of 5-hydroxyphenyl-phenyl-hydantoin. In conclusion, there was no effect of atovaquone on the pharmacokinetics of phenytoin or its major metabolite after a single dose.