Immunoreactivity for calbindin D 28K was localized ultrastructurally in nerve cell bodies and nerve fibres in myenteric ganglia of the guinea-pig small intestine. Reactive cell bodies had a characteristic ultrastructure: the cytoplasm contained many elongate, electron-dense mitochondria, numerous secondary lysosomes that were peripherally located, peripheral stacks of rough endoplasmic reticulum and dispersed Golgi apparatus. The cells were generally larger than other myenteric neurons and had mainly smooth outlines. The cytoplasmic features of these neurons were shared by a small group of immunonegative cells, but the majority of negative cells had clearly different ultrastructural appearances. Of 310 cells from 16 ganglia that were systematically examined, 38% were immunoreactive for calbindin, 10% were unreactive but similar in ultrastructure to the calbindin-reactive neurons and 51% were unreactive and dissimilar in the appearance of their cytoplasmic organelles. Immunoreactive varicosities with synaptic specializations were found on most unreactive neurons, but were markedly less frequent on the calbindin-immunoreactive cell bodies. Non-reactive presynaptic fibres were also more common on non-reactive neurons than on the calbindin-positive cell bodies. Numerous reactive varicosities, some showing synaptic specializations, were found adjacent to other fibres in the neuropil. Light microscopic studies show calbindin immunoreactive neurons to have Dogiel type-II morphology. Thus the present work links distinguishing ultrastructural features to a specific nerve cell type recognized by light microscopy in the enteric ganglia for the first time.