The resistant hepatocyte model was used to investigate the influence of pituitary factors on the early events of chemical carcinogenesis in rat liver. Diethylnitrosamine (DEN), 200 mg/kg body weight, was used as an initiator of enzyme altered foci. Two weeks after initiation the rats were placed on a 0.02% (w/w) 2-acetylaminofluorene (2-AAF) diet for two weeks. Partial hepatectomy (70%) was performed three weeks after initiation. The rats were killed four to six weeks after DEN initiation. Sex differences in area/foci as well as in area ratio (mm2 foci/cm2 liver section) were found in liver sections from sexually mature male and female rats (male greater than female) of both the Sprague-Dawley and Wistar strains. Ectopic pituitary grafts (PG:s) implanted under the kidney capsule of male Wistar rats one week before DEN initiation and removed by unilateral nephrectomy one week after initiation did not influence the number or area of enzyme altered foci as compared with sham operated male rats. On the other hand, PG:s implanted one week before 2-AAF selection in male Wistar rats and allowed to remain until the rats were killed two weeks after the 2-AAF selection period, decreased the area ratio to a level close to that of sham operated female rats, whereas no effect on the number of enzyme altered foci was found. The results suggest that the hypothalamo-pituitary axis may be involved in the regulation of early stages of liver carcinogenesis.