Pancreaticobiliary diversion (PBD) is known to induce chronic, endogenous hypercholecystokininemia causing pancreatic growth in rats. In the present study the proliferative response of the different exocrine pancreatic cells was studied by administration of 3H-thymidine, 1 mCi/kg, given 1 h before the rats were killed and 5, 10, 20, and 40 days after PBD. DNA and 3H-thymidine uptake, both expressed per 1 mg of pancreatic tissue, were significantly increased on day 5. The nuclear labeling index was increased fivefold in both the acinar and ductal cell group. In the centroacinar cell group the labeling index was increased on day 10. In conclusion, we found that the proliferative activity after PBD occurred during the first 10 days and that the ductal cells were forced into proliferation to the same extent as the acinar ones. These findings are of interest for future studies of hormonal influences on the development of pancreatic carcinoma.