The pharmacokinetics of ethosuximide were studied in dogs and compared with the data known for man. After intravenous injection of 40 mg/kg to 9 dogs, the concentration-time curve in serum could be described by the open one-compartment model. Serum half-lives were between 11 and 25 hr, the volume of distribution correspond to between 44 and 66% of body weight. After oral administration of the same dose, maximal serum concentrations were reached within 1-4 hr and the absorption amounted to 88-95%. By treatment with three daily doses, a plateau in serum concentrations could be reached and maintained. At serum concentrations above 100 microliter/ml, half-lives seemed prolonged when compared to the values determined previously with a dose of 40 mg/kg. Ethosuximide rapidly enters the cerebrospinal fluid, equilibrium was established after 20-30 min. Plasma protein binding of the drug was negligible. Comparison of the pharmacokinetic data for dog and man reveals, in spite of the somewhat shorter half-life in the dog, a rather good agreement. In female rats, ethosuximide had an average half-life of 10 hr, in mice of hardly 1 hr. Concentrations in serum and brain of mice equilibrated within 10 min.