Pancreatic acinar cell turnover was studied after a 48-h fast and in rats fed raw soya flour (RSF) for up to 28 days. Feeding RSF for 2 days resulted in a significant increase in pancreatic weight and RNA content while protein was increased by the 4th day compared with rats fasted for 48 h. RSF also resulted in a significant increase in RNA by the 4th day and weight and protein by the 7th day compared with rats fed heated soya flour (HSF). This pancreatic hypertrophy was maintained for the rest of the study period. Two days after starting RSF, pancreatic DNA synthesis, measured by the rate of incorporation of [3H]thymidine into pancreatic DNA, had increased sixfold compared with that in animals fed HSF but returned to control values again by the 4th day on the diet. Autoradiography showed that this increase in DNA synthesis occurred in both acinar and duct cells, with turnover in acinar cells preceding that in duct cells. A second more gradual rise in DNA synthesis was seen from the 7th to 28th day. This peak in DNA synthesis was associated with an increased total pancreatic DNA content and occurred predominately in duct cells with a smaller contribution from acinar cells. Histological studies of the pancreas during the 1st wk showed cell damage and tissue necrosis, possibly due to exposure to high levels of cholecystokinin released by RSF. The first peak in DNA synthesis may be a regenerative response to this damage. The second more delayed peak appears to be hyperplasia in response to a trophic stimulus, again possibly mediated by cholecystokinin.