This study was undertaken to evaluate the effects of caerulein, a CCK analog, on the different cell populations of the pancreatic tissue and their respective turnover. Rats received saline or caerulein subcutaneously and 3H-thymidine intraperitoneally three times a day for 4 days. They were sacrificed immediately after termination of treatment and 2, 15 and 50 days later. With age, the proportion of acinar cells decreased significantly whereas those of the ductal and interstitial cells increased. Although caerulein induced preferential acinar cell growth, it did not modify the proportion of this cell population with regard to the other cells. However, at specific times after termination of treatment, caerulein induced modifications in the ductal, endothelial and interstitial cell populations. The growth promoting effect of caerulein was evident from the specific increases in total DNA content and DNA synthesis. The labeling indices indicate that all cell populations except the endocrine system were stimulated to grow in response to caerulein. Furthermore, all new cells remained for at least 50 days after termination of treatment. These data indicate that caerulein induced uniform growth of the pancreatic tissue during intensive treatment. The normal growth rate of these stimulated cells was, however, arrested for the following 50 days while that of the control group cell population proceeded normally.