Epidermal growth factor (EGF) is a mitogenic stimulus in many tissues and occurs in large amounts in the pancreas and salivary glands. Whether EGF is mitogenic in the pancreas is controversial, and the EGF effect has not been studied in the salivary glands. Therefore, the aim of the present study was to investigate the possible effects on the pancreas and parotid and submandibular glands at different time intervals after exogenous EGF administration. Human recombinant EGF was infused subcutaneously by osmotic minipumps in three groups of mice (for 1, 3, and 7 days, respectively) at a dosage of 10 micrograms/kg/h (1.6 mumol/kg/h). Tritiated thymidine was infused intraperitoneally by osmotic minipumps for the same time periods, but only for the last 3 days in the 7-day group. After 1 day the pancreas increased in weight and the increase persisted throughout the study. No effect was seen on the parotid or submandibular gland wet weight. A slight transient increase in pancreas protein content was observed, whereas amylase content was unaffected. The labeling index of serous and ductal cells in the parotid gland increased from the third day. After 7 days, all cell types studied in the pancreas and parotid and submandibular glands were in a hyperproliferative state. The results show that EGF evoked a strong proliferative response on all cell types studied in the pancreas and parotid and submandibular glands.