The objective of the study was to compare the bioavailability of a single oral 200-mg dose of four brands of phenytoin sodium available in the Indian market. Dilantin, Epsolin, and M-toin were compared with Eptoin, which was taken as the reference standard. A randomized, assessor-blind, four-way crossover study was done in 12 healthy Indian volunteers. The study was conducted at a clinical pharmacology ward at King Edward VII Memorial Hospital, a tertiary referral center in Mumbai (Bombay). All 12 subjects received a single oral 200-mg dose of all the formulations with a 2-week washout period between the formulations. Blood samples for plasma phenytoin levels were collected at 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours. Safety was measured by pretreatment and posttreatment biochemical investigations, physical examination, and ECG. The pharmacokinetics of the four brands of phenytoin were calculated by maximum plasma concentration (C(max)), time to reach C(max) (t(max)), area under the concentration versus time curve for time 0 to 72 hours (AUC(0-72)), and from time 0 to infinity (AUC(0- infinity)). For all brands, 90% CI of all untransformed and log transformed pharmacokinetic parameters failed to remain within prescribed limits of 80% to 120% for untransformed data and 80% to 125% for log transformed data. Since phenytoin obeys Micheles Mentens kinetics, the AUC methodology used for comparison would give only an approximate indication of relative bioavailability. M-toin was shown to be bioinequivalent to Eptoin. The other comparisons indicate but do not prove bioinequivalence of the other brands. The results of the study show that in India switching phenytoin brands could have significant implications and is not advisable once a patient is carefully titrated on one formulation.