Ketanserin, a selective serotonin (5-HT) antagonist at 5-HT2 receptors, was investigated in a 3-month, double-blind, placebo-controlled study in twenty patients with intermittent claudication. Blood-pressure ratio (thigh/arm), reactive hyperaemia measured with an ECG-triggered venous occlusion plethysmograph, blood filterability, and claudication distance on a treadmill progressively and significantly improved during ketanserin therapy, whereas no such changes occurred in the placebo group. Mean claudication distance improved by 140%; four of the eleven patients on ketanserin were able to keep walking beyond the time limit of the exercise test. The beneficial effect of ketanserin suggests that 5-HT may be involved in the pathogenesis of peripheral arterial obstructive diseases. In an experiment comparing blood-pressure ratio measured by doppler velocimetry and by plethysmography, the plethysmographic values rose during ketanserin therapy only at thigh level, which suggests an improvement in the collateral circulation.