In heat-acclimated rock pigeons, cutaneous water evaporation is the major cooling mechanism when exposed at rest to an extremely hot environment of 50-60°C. This evaporative pathway is also activated in room temperature by a -adrenergic antagonist (propranolol) or an -adrenergic agonist (clonidine) and inhibited by a -adrenergic agonist (isoproterenol). In contrast, neither heat exposure nor drug administration activates cutaneous evaporation in cold-acclimated pigeons. To elucidate the mechanisms underlying this phenomenon, we studied the role of the ultrastructure and permeability of the cutaneous vasculature. During both heat stress and the administration of propranolol and clonidine, we observed increased capillary fenestration and endothelial gaps. Similarly, propranolol increased the extravasation of Evans blue-labeled albumin in the skin tissue. We concluded that heat acclimation reinforces a mechanism by which the activation of adrenergic signal transduction pathways alters microvessel permeability during heat stress. Consequently the flux of plasma proteins and water into the interstitial space is accelerated, providing an interstitial source of water for sustained cutaneous evaporative cooling.