The purpose of this study was to determine whether pancreatic ductal epithelium has trophic effects on the islets of Langerhans, and how this intercellular communication might be mediated. Islets and ducts were isolated from hamster pancreata. Islets were purified on a bovine serum albumin gradient. Primary duct cultures were passaged twice for cell purification. Duct-conditioned medium (DCM) was collected from duct cultures passaged twice. The islets were allocated to three experimental groups: (1) 100 islets alone; (2) 100 islets + 80 tertiary ducts and (3) 100 islets in 25% DCM. All tissues were embedded in rat tail collagen for the duration of the study. The influence of pancreatic ductal epithelium on islet cell death (necrosis and apoptosis), islet morphology, and islet-cell proliferation was examined. As determined by inverted microscopy, 17.3% $ pm$ 1.8 of the islets cultured alone, demonstrated central necrosis, in comparison to 4.6% $ pm$ 1.0 of the islets co-cultured with ducts (p $<$ 0.05). Specific cell death detection ELISA indicated that DNA fragmentation in islets cultured alone (0.23 $ pm$ 0.04), was significantly increased compared to islets cultured with ductal epithelium (0.09 $ pm$ 0.02) (p = 0.03). At 27$ sp circ$C, 60.5% $ pm$ 8.8 of the islets cultured alone showed peripheral cell disintegration, in contrast only 2.6% $ pm$ 0.3 (p $<$ 0.001) of the islets cultured with ducts. Tritiated thymidine incorporation into islets cultured with ducts (235.8 $ pm$ 33.9) was 120% higher than that in islets cultured alone (96.3 $ pm$ 18.8) (p = 0.01). Similar results were obtain from the third experimental group, when ductal epithelium was substituted with DCM. In conclusion, pancreatic ductal epithelium can stimulate islet cell survival and growth. This effect appears to be mediated in a paracrine manner by the release of factor(s) from the ductal cells into the media.