Although it is known that doublets of hepatocytes GST-P+ are produced during the first week after initiation with DEN, the activity levels of the enzyme are not known in the initial stages of the process, neither is its behavior through an initiation-promotion scheme. We consider the latter issues important in order to obtain information of the initiation step and its relation with GST-P.DEN was applied as initiator in a single dose on day 0 to F344 rats (200 mg/kg) and as promoter 2-AAF in 20 mg/kg doses on days 7, 8 and 9 of the scheme. Partial hepatectomy was performed on day 10, and daily during the 28 days in which the experiment lasted. The GST-P activity was determined in postmicrosomal supernatants of respective livers (by immunoadsorption) as well as their histological section (by immunohistochemistry). In both cases antibody anti-GST-pi produced in our laboratory was employed. The results obtained show GST-P appearance on day 5 of the scheme in rats treated with carcinogens. The activity of the enzyme increased slowly reaching its maximum on day 18, together with the appearance of GST-P+ preneoplastic nodules. Our results suggest that GST-P could display an additional function to those previously known, in cellular differentiation this could explain the very frequent expression of this enzyme in preneoplastic as well as in neoplastic cells.