We describe a sensitive and precise method for the simultaneous high pressure liquid-chromatography determination of phenobarbital, diphenylhydantoin, primidone, and carbamazepine in serum. The drugs are extracted into chloroform, dried and dissolved in the mobile phase. The drugs are eluted from a reverse-phase column with methanol/water and detected by their absorption at 214 nm. Concentrations are estimated from their peak heights.The results, when compared with those by enzyme-immuneassay, gave correlation coefficients of 0.990 for phenobarbital, 0.993 for diphenulhydantoin, 0.992 for primidone and 0.994 for carbamazepine.