A recently developed system for measuring antiepileptic drug concentrations was evaluated for phenytoin and phenobarbital. The apoenzyme reactive immunoassay system was compared with gas-liquid chromatography, EMIT, and TDX systems. Comparisons were performed with control specimens and with sera obtained from patients at three facilities. Precision for all methods was similar, with within-run and between-run coefficients of variation generally 5%. The accuracy of all methods was acceptable, but bias was present in some. However, measurements obtained by a nontechnical person (physician) in a clinical setting were sometimes inaccurate.