In superfusion experiments on isolated porcine coronary arterial and venous ring preparations precontracted by prostaglandin F2 alpha repeated bolus application of carbon monoxide induced a reproducible relaxation. The vessels were rubbed to remove the endothelium, 30 min superfusion with 10(-5) M of 8-bromocyclic-GMP decreased the tension in coronary artery and vein and reduced the carbon monoxide response in the latter. Methylene blue increased the tone and inhibited the carbon monoxide effect in both vessels. The results show that carbon monoxide relaxing action on vascular smooth muscle might be due to activation of guanylate cyclase similar to the action on nitric oxide and/or endothelium-derived relaxing factor.