Samples of normal and pathological human liver were assayed for microsomal epoxide hydrolase activity using the chlorinated epoxide HEOM as substrate. The enzyme activity in liver samples from normal patients was 72.3 +/- 9.8 nmoles mg protein-1.min-1, which is comparable to the highest values recorded in mammals, and much higher than those found in rats and mice. A microassay procedure was developed to enable the estimation of activity in needle biopsy samples (5-20 mg), obtained from patients with normal and diseased livers. Three epileptic patients who had received regular doses of phenobarbitone and/or phenytoin showed activities significantly higher than those found in all other samples (P less than 0.01). These appeared to be examples of enzyme induction. Assays were also performed on samples from six patients with alcohol-related liver disease and one patient with hepatocellular carcinoma. The role of epoxide hydrolase in the metabolism of carcinogenic epoxides is discussed in relation to these findings.