The decline in arterial systemic blood pressure which follows the initial rise during i.v. perfusion of L-noradrenaline in normal rats has been compared with the same type of decline induced by metaraminol or phenylephrine, both alpha-sympathomimetic drugs (acute tolerance or escape). Vasoconstrictor activity of noradrenaline in shot i.v. injection is regularly decreased when acute tolerance develops. This hyposensitivity to NA indicates that a change in alpha-receptor affinity for circulating NA may explain the acute tolerance as well as the noradrenaline escape.