The transfer of the antiepileptic drug valproic acid (2-propyl-pentenoic acid) and one of its active metabolites, 2-en (2-propyl-2-pentenoic acid) from plasma to brain and liver were studied in mice at low dose levels (0.1, 0.3, 0.7, and 1.0 mmole/kg). The liver concentrations of 2-en were found to be lower than those of VPA: the liver/plasma ratios of 2-en for the four doses were 0.1, 0.2, 0.3 and 0.8, respectively; for VPA the corresponding liver/plasma ratios were 3, 2, 1.2 and 1.0, respectively. Following doses of 0.1-0.7 mmole/kg, plasma protein binding of 2-en (free fractions 2-7%) was much more extensive than of VPA (free fractions 40-45%). Also in the rat the liver/plasma concentration ratios of 2-en (0.3) were much below those of VPA (0.6). In mice, brain concentrations of 2-en were approximately 1/2 of corresponding plasma levels. Our results indicate that the transfer of 2-en into liver is limited by extensive protein binding of this compound in plasma.