Dexamphetamine contracted isolated preparations of rat stomach, dog retractor penis, rabbit aorta, rabbit uterus and all sections of guinea-pig ileum. Adrenaline inhibited rat stomach and all but the terminal 10 cm of guinea-pig ileum, but contracted dog retractor penis, rabbit aorta, rabbit uterus and the terminal portion of the guinea-pig ileum. 5-Hydroxytryptamine contracted all five preparations. Responses to dexamphetamine and 5-hydroxytryptamine were not blocked in preparations protected by a high concentration of either drug during exposure to phenoxybenzamine in a dose which usually caused block. Responses to dexamphetamine and 5-hydroxytryptamine were blocked in preparations protected by adrenaline. Responses to dexamphetamine in dog retractor penis, rabbit aorta and rabbit uterus were not reduced in preparations from animals treated with reserpine or after cocaine, indicating that the contraction is not mediated by released noradrenaline. It is concluded that dexamphetamine acts directly on 5-hydroxytryptamine receptors in these smooth muscles and therefore cannot be regarded as a true sympathomimetic amine.