5‐Hydroxytryptamine (5‐HT) contracted isolated saphenous vein strips of the dog, producing a biphasic concentration‐effect curve. The first phase occurred with low concentrations of 5‐HT (1.0 × 10−8 to 5.0 × 10−6mol/1) with a plateau between 1.0 × 10−6mol/1 and 1.0 × 10−5mol/1. The second phase occurred with high concentrations of 5‐HT (greater than 1.0 × 10−5 mol/1). The α‐adrenoceptor antagonists, phentolamine (5.0 × 10−8 to 5.0 × 10−7 mol/1), labetalol (1.0 × 10−6 to 1.0 × 10−5 mol/1) and thymoxamine (1.0 × 10−6 to 1.0 × 10−5 mol/1), antagonized responses to high concentrations of 5‐HT but responses to low concentrations of 5‐HT were not antagonized. The effects of high concentrations of 5‐HT were antagonized by cocaine (1.0 × 10−6 to 1.0 × 10−5 mol/1) and were not evident in veins removed from dogs pretreated with syrosingopine. It is concluded that in the saphenous vein, low concentrations of 5‐HT act directly on specific 5‐HT receptors and that high concentrations of 5‐HT also act indirectly on α‐adrenoceptors by displacing noradrenaline from neuronal stores. 1978 British Pharmacological Society