The occurrence, effects and sensitivity to capsaicin and stimulation of adenylate cyclase of calcitonin gene-related peptide (CGRP) in the rat kidney have been investigated. CGRP-like immunoreactivity was higher in the medulla than in the papilla and the cortex. Capsaicin pretreatment significantly reduced CGRP-like immunoreactivity in the medulla and papilla while a small reduction was found in the cortex. CGRP-immunoreactive nerve fibres were observed surrounding blood vessels and occasionally in the vicinity of renal tubules and between the collecting ducts in the papilla. Some CGRP-immunoreactive fibres were also seen in kidneys from capsaicin-pretreated rats. Infusion of capsaicin (1 microM) through the renal artery of isolated and perfused rat kidney increased the CGRP-like immunoreactivity outflow from the venous effluent. This effect exhibited desensitization at the second challenge with the drug. Infusion of either capsaicin (1 microM) or CGRP (1 microM) reduced the increase of perfusion pressure induced by norepinephrine in isolated perfused rat kidney. Plasma protein extravasation was studied in the various regions of the rat kidney following infusion of capsaicin. No significant change was observed in the medulla, papilla or cortex after capsaicin administration. Adenylate cyclase activity was studied in membrane preparations from cortex, medulla and papilla of rat kidney. Cortical and medullary adenylate cyclase was stimulated in a concentration-dependent manner by salmon calcitonin, rat calcitonin and rat CGRP. Salmon calcitonin in these two areas showed half-maximal effective concentration approximately 1000 times lower and maximal stimulation only slightly higher than those of rat calcitonin and rat CGRP. However, in the papilla, only rat CGRP was able to induce a 60% increase of enzyme activity (half-maximal effective concentration, 19 +/- 1.6 nM). It is concluded that CGRP contained in capsaicin-sensitive sensory nerve may exert a local function in discrete areas of the rat kidney.