The ␣ 1a -adrenergic receptor (␣ 1a AR) occupies intracellular and plasma membranes in both native and heterologous expression systems. Based on multiple independent lines of evidence, we demonstrate the ␣ 1a AR at the cell surface occupies membrane rafts but exits from rafts following stimulation. In nondetergent raft preparations, basal ␣ 1a AR is present in low density membrane rafts and colocalizes with its G protein effectors on density gradients. Raft disruption by cholesterol depletion with methyl-␤-cyclodextrin eliminates these light rafts. To confirm the presence of the ␣ 1a AR in plasma membrane rafts, fluorescence resonance energy transfer measurements were used to demonstrate colocalization of surface receptor and the raft marker, cholera toxin B. This colocalization was largely lost following ␣ 1a AR stimulation with phenylephrine. Similarly, receptor stimulation causes exit of the ␣ 1a AR from light rafts within 3-10 min in contrast to the G proteins, which largely remain in light rafts. Importantly, this delayed exit of the ␣ 1a AR suggests acute receptor signaling and desensitization occur entirely within rafts. Interestingly, both confocal analysis and measurement of surface ␣ 1a AR levels indicate modest receptor internalization during the 10 min following stimulation, suggesting most of the receptor has entered non-raft plasma membrane. Nevertheless, activation does increase the rate of receptor internalization as does disruption of rafts with methyl-␤-cyclodextrin, suggesting raft exit enables internalization. Confocal analysis of surface-labeled hemagglutinin-␣ 1a AR reveals that basal and stimulated receptor occupies clathrin pits in fixed cells consistent with previous indirect evidence. The evidence presented here strongly suggests the ␣ 1a AR is a lipid raft protein under basal conditions and implies agonist-mediated signaling occurs from rafts.