The mesenchymal capsule was removed from the epithelial anlage of 15 day (unbranched) and 16 day (initially branched) fetal rat submandibular gland (SMG) rudiments. The undifferentiated epithelial portion of the SMG rudiments was placed in tissue culture and examined by light and electron microscopy and histochemistry for secretory peroxidase. The 15 day fetal SMG epithelial rudiments failed to attach, and spread over the culture dish and degenerated by 3 days in culture. The 16 day epithelial rudiments attached to the dish and the cells spread radially from the explant. Mitotic activity was minimal. Cells spreading from the 16 day rudiments underwent cytodifferentiation, giving rise to two secretory cell types: (1) peroxidase containing “proacinar cells,” and (2) secretory “terminal tubule” cells. The results suggest that in the developing SMG, morphogenesis and cytodifferentiation are partially coupled but independently regulated processes. The earliest phases of morphogenesis (rudiment down growth and primary branching) seem to be required to initiate cytodifferentiation. Once initiated, cytodifferentiation can proceed in the absence of continued morphogenesis (tissue organizatation) or significant amounts of connective tissue elements.