Calcitonin gene-related peptide (CGRP)-containing nerve fibres were identified by pre- and post-embedding electron-microscopic immunocytochemistry in the guinea-pig small intestine. Immunoreactive nerve processes were numerous in the mucosa and submucosa, especially in the connective tissue among the crypts of Lieberkühn. In some cases they were found in close apposition to epithelial cells. Many of the labelled nerve fibres were observed around blood vessels, especially arterioles. In the inner circular muscle layer, the immunoreactive nerve processes were found in close association (sometimes less than 40 nm) to smooth muscle cells. CGRP-positive terminals contained a predominance of electron-lucent synaptic vesicles (35-40 nm in diameter) together with a few large granular vesicles (80-120 nm in diameter). Post-embedding immunostaining, using the immunogold procedure, localized CGRP-immunoreactivity in large granular vesicles, 80-92 nm in diameter. These ultrastructural observations confirm that CGRP-containing nerve fibres exist in the small intestine and suggest that they may participate in the regulation of the smooth muscle activity, mucosal cell secretion and blood flow and, by analogy with other systems, a sensory role also seems likely.