OBJECTIVE: Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role of CGRP in the control of vasodilation in the coronary circulation. METHODS: 12 patients (mean age 60 years) performed exercise tests on consecutive days during intravenous infusions of placebo or CGRP (at 50 pmol.min-1). At cardiac catheterisation (6 patients), consecutive 20 min intravenous infusions of placebo and CGRP were given at a fixed heart rate, with measurement of haemodynamic variables and quantitative arteriography. RESULTS: The time to 0.1 mV ST depression increased from 475(SD 245) to 546(193) s (p < 0.05), and time to 0.2 mV ST segment depression, from 634(266) to 694(202) s (p < 0.05), on placebo and CGRP respectively. Rate-pressure product at 0.1 mV ST segment depression was 18,410(4590) and 20,750(7270) mm Hg.min-1 (p < 0.05), and at 0.2 mV ST depression it was 21,510(6470) and 24,080(7380) mm Hg.min-1 (p < 0.01), with placebo and CGRP, respectively. At catheterisation, diastolic blood pressure fell from 93(11) to 83(8) mm Hg (p < 0.05), systemic vascular resistance fell from 26.2(9.4) to 20.7(9.0) units (p < 0.05), and cardiac output increased from 5.94(1.10) to 6.73(1.04) litre.min-1 (p < 0.05), on placebo and CGRP respectively. Minimum luminal diameter increased from 0.66(0.23) to 1.11(0.15) mm (p < 0.01) with CGRP. CONCLUSIONS: Intravenous CGRP is a systemic arterial vasodilator which dilates coronary arteries at the site of atheromatous stenoses and delays the onset of myocardial ischaemia during treadmill exercise testing in patients with chronic stable angina.