1. For several years we have been working on the synthesis of modified hydrazinopyridazines which have proved to possess remarkable vasorelaxant and antihypertensive activity. We now report the vasodilator effects of three novel 6-aryl-5-piperidino-3-hydrazinopyridazines (1a, 1b and 1c), structurally related to the well-known antihypertensive drug hydralazine. 2. Hydralazine and the new hydrazinopyridazines relaxed, in a concentration-dependent and nonspecific way, the contractions elicited by noradrenaline or a high K+ concentration in rat aortic rings with or without endothelium. According to the IC50 (50% inhibitory concentrations) values obtained, the vasorelaxant potency of the new compounds was greater than that of hydralazine. 3. In a Ca2+-free medium, the contractions provoked by noradrenaline or caffeine were significantly inhibited by the new hydrazinopyridazines and by hydralazine. 4. Hydralazine and the novel molecules did not significantly modify basal, noradrenaline- or K+-induced 45Ca2+ uptake. 5. These results suggest that 1a, 1b and 1c have an endothelium-independent vasorelaxant activity greater than that of hydralazine in isolated rat aortic rings, which seems not to be mediated by a blockade of transmembrane Ca2+ movements through specific channels. This effect could be due, at least in part, to an intracellular mechanism of action.