1The role of corticosterone, a potent in vitro inhibitor of extraneuronal uptake, in the regulation of the extraneuronal accumulation of [3H]-isoprenaline into rat atria was examined. 2 Procedures which increased plasma corticosterone levels resulted in a decrease in the corticosterone-sensitive component of extraneuronal accumulation of [3H]-isoprenaline (64% after reserpine treatment and 25% after chronic cold exposure). 3 Procedures which decreased levels of plasma corticosterone resulted in an increase in the corticosterone-sensitive component of extraneuronal accumulation of [3H]-isoprenaline (approximately 20% after adrenalectomy and 32% after hypophysectomy). This increase was partially prevented by the in vivo administration of dexamethasone (40 pg kg-'). 4 There was a strong inverse correlation between the plasma corticosterone concentration and the level of extraneuronal uptake into atria (P <0.01). 6 Corticosterone appears to play a major role in the regulation ofextraneuronal uptake into tissues of the rat.