The concentrations of phenobarbitone, albumin, bile acids and cholesterol, and the activities of alkaline phosphatase (AP), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) and glutamate dehydrogenase (GLDH) were measured in the serum of 95 epileptic dogs whose clinical signs were controlled with phenobarbitone. The dogs were divided into groups on the basis of the concentration of phenobarbitone in their serum, the dose administered and the duration of the treatment. The concentration of phenobarbitone in serum was directly related to the activities of ALT, AP, GGT and GLDH and inversely related to the concentration of albumin. There was no significant relationship between the duration of treatment and the serum concentration of phenobarbitone, but there was a significant relationship between the duration of treatment and the activities of ALT, AP and GLDH. Thirty-five of the dogs (37 per cent) had serum activities of AP above the normal range, 19 had abnormally high activities of ALT, and 15 had high activities of GLDH, but these incidences were not related to the serum concentration of phenobarbitone. The dogs receiving higher doses for longer periods had the highest incidence of high activities of AP, ALT and GLDH. The concentration of bile acids in seven of the dogs was above the normal range but there was no relationship between the concentration and either the serum concentration, dose or duration of treatment with phenobarbitone.