The small GTP-binding protein, rab4, is involved in recycling of transferrin receptors and translocation of GLUT4. Recent studies suggest that rab4 controls regulated exocytosis in the exocrine pancreas. We conducted the present study to further investigate the role of rab4 in the exocrine pancreas. We found that the exocrine pancreas expresses two rab4 immunoanalogs, one of similar to 28 kDa identified previously in neonatal glands, and one of similar to 24 kDa which is similar to rab4 characterized in other systems. The latter species was mostly membrane-anchored and localized to endosome-like structures in a supranuclear region that was immunopositive for the transferrin receptor. The similar to 24-kDa rab4 form also localized to the apical plasmamembrane, and this immunofluorescence increased greatly in tissue challenged with a secretagogue. We propose that the similar to 24-kDa rab4 species is involved in compensatory membrane retrieval following regulated exocytosis, and that rab4-positive endocytic vesicles move through a supranuclear recycling compartment.