Twenty-seven epileptic patients, most from low socioeconomic groups and aged 15-54 years, were studied for effects of prolonged anticonvulsant medication. They had received the usual doses of phenobarbitone and diphenylhydantoin (PHT) regularly for 3-32 years, with control of seizures, and had not taken any B-vitamins in the year before investigation. Besides reduced serum and cerebrospinal fluid (CSF) folate levels, significantly increased levels of total vitamin B6 in CSF and serum and of vitamin B12 in serum were found in patients as compared with normal healthy subjects. The bone marrow was normoblastic, and significant elevation of serum triglycerides and/or cholesterol was observed in patients. The total protein level was only slightly reduced as compared with that of controls, but there was significant increase in beta-lipoprotein fraction on gel electrophoresis. Plasma proteins concerned with vitamins and lipid transport showed no remarkable change, and no abnormal protein was detected. Although there was no clinical hepatic involvement, liver biopsy performed in 9 of 27 patients revealed fine structural changes in hepatocytes suggestive of varying degrees of drug-induced changes. A ramifying network of short, smooth, endoplasmic cisternae with depleted rough endoplasmic reticulum (RER), distended sinusoids with Kupffer cells, dark shrunken hepatocytes with reduced mitochondria, and increased lipofuscin were observed. This suggested an adaptive response of the liver, a reversible change, possibly related to the increased serum lipids in the same patients.