Rats were fed purified diets which provided 24% protein from casein (C), soy protein isolate (SPI), or egg white (EW) for 18 mo. Groups of rats were killed at 3, 6, 12 and 18 mo; the pancreata were removed and examined histologically for occurrence of atypical nodules. The weight, protein, DNA, trypsin and chymotrypsin concentrations of the pancreas at each period were measured. Over the entire experimental period, body weight did not differ among groups. Pancreatic weight, protein and trypsin activity were highest in the EW group, followed by the SPI group, and lowest in the C group. Chymotrypsin activity was significantly higher in the EW and SPI groups than the C group. DNA content did not differ significantly among groups over the entire experimental period, although it was elevated in the SPI or EW groups compared to the C groups at some of the time periods. Only one microscopic nodule was observed in all of the animals; it was found at 3 mo in the pancreas from an animal fed EW. Overall, the results suggest that the elevation in enzyme activity and pancreatic weight associated with long-term consumption of EW and SPI did not result in development of pancreatic lesions in rats.