Interactions between SP and the enkephalins have bben reported in the CNS, and the possibility of a more peripheral site of interaction has now been investigated. SP (10(-6) - 10(-4) g/ml) induced dose-related contractions of the rabbit isolated aorta, which were resistant to alpha-adrenoceptor blockade (phentolamine, 5 x 10(-6) g/ml). Neither met- nor leu-enkephalin had any intrinsic action on the aorta, but met-enkephalin at 5 x 10(-6) g/ml significantly inhibited responses to SP but not to NE. Morphine (5 x 10(-6) g/ml) potentiated responses to NE, but had no significant effect on responses to SP. It is apparent that SP and met-enkephalin act on a common receptor on vascular smooth muscle, that met-enkephalin has no intrinsic action on this receptor, and that the receptor is morphine-insensitive.