The effect of local administration of calcitonin gene-related peptide (CGRP) on sweating activity was evaluated on normal human volunteers. CGRP and methacholine chloride (MCH) was dissolved in 0.1 ml of 0.9% NaCl solution to a specified concentration, and was injected intradermally at the center of a 1.3 cm2 forearm test area. The sweat rate was recorded continuously by capacitance hygrometry in a relatively cool environment (Ta, 23 degrees C). CGRP did not elicit any sweat secretion when administrated by alone, but significantly increased the sweat rate when it was administrated with MCH. The maximum enhancement of MCH-induced sweating by CGRP was observed at a concentration of 10(-5) g/ml of CGRP. There was clear dose-dependent relationship between the dose of CGRP and its enhancement. Recently, CGRP-like immunoreactivity is demonstrated to be present in cholinergic nerve terminals around the human sweat glands. These observations have strongly suggested that CGRP enhances the cholinergic sweating activity. Although the underlying mechanism is still obscure, CGRP may enhance the sweating as a consequence of vasodilation which has been known to be a major activity of CGRP. As for the evaluation of human sweat gland function, CGRP-induced peptidergic regulation should be considered as well as cholinergic regulation.