133Xenon clearance represents a clinically useful method of measuring local circulatory function in a variety of different tissues. The method detailed in this article describes how the 133Xenon clearance technique can be adapted to simultaneously measure cutaneous blood flow, over a 15-min period, at a large number of skin sites within the same animal. Blood flow changes are measured in response to intradermally injected vasoactive test agents. The multisite injection plan which forms part of the method removes bias due to site variations and generates data that can be analysed statistically. Results are expressed as the percent change in 133Xenon clearance at test agent-injected sites as compared to control, saline-injected sites. The method provides an accurate and time-efficient measure of skin blood flow. In the present study, the technique is used to assess the receptor-mediated mechanism of action of the vasodilator calcitonin gene-related peptide (CGRP) and the possibility that the vasoconstrictor endothelin-1 acts to stimulate the release of vasodilator quantities of endogenous CGRP.