Receptor-mediated increases in intracellular Ca²⁺ levels can be caused by release from intracellular organelles and/or influx from the extracellular fluid. Noradrenaline (NA) released from sympathetic nerves acts on α₁-adrenoceptors to increase cytosolic Ca²⁺ and promote smooth muscle contraction¹. In many cells activation of α₁-adrenoceptors causes formation of inositol 1,4,5-trisphosphate which promotes Ca²⁺ release from intracellular stores^2,3. The mechanism by which receptor activation opens cell surface Ca²⁺ channels is not known, although in some cases it may be secondary to formation of inositol phosphates^4,5 or release of stored intracellular Ca²⁺ (ref. 3). However α₁-adrenoceptors have recently been shown to have different pharmacological properties in different tissues^6–9, and it has been proposed that different α₁-adrenoceptor subtypes may control mobilization of intracellular Ca²⁺ and gating of extracellular Ca²⁺ influx^7,9,10–12. We here report evidence for two subtypes of α₁-adrenoceptors which cause contractile responses through different molecular mechanisms. One subtype stimulates inositol phosphate (InsP) formation and causes contractions which are independent of extracellular Ca²⁺, and the other does not stimulate inositol phosphate formation and causes contractions which require the influx of extracellular Ca²⁺ through dihydropyridine-sensitive channels. These results suggest that neurotransmitters and hormones may control Ca²⁺ release from intracellular stores and influx through voltage-gated membrane channels through distinct receptor subtypes.