A highly sensitive assay for the epoxide hydrolase activity associated with the preneoplastic antigen (PNA) has been developed based on the synthesis of cis-stilbene oxide labeled with tritium at approximately 15 Ci/mmol. This assay allows the detection of elevated epoxide hydrolase activity in the serum of humans and rodents as well as in the culture medium bathing isolated hepatocytes. The integrity of the enzymatic assay was confirmed in rodents by precipitating the serum PNA activity using an antibody raised against the rat microsomal epoxide hydrolase. Methodology for the detection of PNA in serum will facilitate evaluation of this antigen as a marker for hepatic neoplasia in man and in experimental animals.