A rapid isothermal method has been developed for felbamate quantitation in human serum. Felbamate and internal standard (2-methyl-2-phenyl-1,3-propanedioldicarbamate) are isolated from alkalinized serum into methylene chloride with a single 90-s extraction. A further concentration step is unnecessary. Three microliters of the sodium sulfate-dried extract is injected into a GC equipped with a 30 m x 0.25 mm DB-1 column with a 0.25 microns film operated in split mode. Detection is by flame ionization. Thermal degradation of the carbamates has been minimized and is reproducible. Multiple-analyst day-to-day coefficient of variation = 3.25% (n = 130) at a felbamate concentration of 25 mg/L and 2.18% (n = 129) at 100 mg/L. The method is linear to 250 mg/L and the lowest concentration to be consistently integrated by the data system was 2.0 mg/L. No significant interferences were found from 60 commonly encountered drugs. Serum felbamate concentrations ranged from 3 to 137 mg/L (n = 212, mean = 56 mg/L) when assayed by this method, which is suitable for therapeutic drug monitoring, pharmacokinetic studies, and overdose monitoring.