Somatostatin from gastric D-cells exerts an inhibitory effect upon the release of gastric acid, enzymes and gastrin. From previous investigations, a paracrine mode of action of somatostatin has been postulated. However, the exact route of the delivery of gastric somatostatin remains still uncertain and controversial. To obtain a closer view of fundic D-cells, the complete shapes and their microanatomical relationships to neighboring tissue elements were examined in immunostained serial semithin (0.5 mu m) sections of the fundic mucosa of rats, mice and golden hamsters, exemplarily by the combined utilization of computer-assisted 3D reconstructions. All the D cells examined in the present study were found to belong to the 'closed-type' of entero-endocrine cells lacking contiguity to the luminal surface. In their shape, the D cells in this region displayed an expressed 'pleomorphism'. A subpopulation of D cells, ovoid in shape, were thoroughly enclosed by single parietal cells. Most of the D cells appeared to be intimately juxtaposed to parietal cells and/or chief cells with their cell bodies or cytoplasmic processes, but simultaneously blood capillaries were regularly located in close vicinity to such D cells. Thus, somatostatin from the fundic D cells may act upon parietal cells and chief cells via both paracrine (direct cell to cell or diffusion) and endocrine (local circulatory system). The morphological heterogeneity of gastric fundic D cells may reflect certain functional states.