Experiments were performed to investigate the effect of moderate cooling on adrenergic neuroeffector interaction in canine cutaneous veins. Helical strips of dog's saphenous vein, untreated or first incubated with 3H-norepinephrine were mounted for superfusion and isometric tension recording; the overflow of endogenous catecholamines or 3H-norepinephrine and its metabolites, respectively, were measured in the superfusate. In other experiments the monoamine oxidase activity or the catechol-O-methyltransferase (COMT) activity of the saphenous vein wall was determined. Moderate cooling (from 37 to 24 degree C) decreased the evoked release of endogenous norepinephrine during electrical stimulation of the adrenergic nerve endings in the blood vessel wall. Moderate cooling depressed the overflow of 3H-norepinephrine and its metabolites in unstimulated preparations, during electrical stimulation during superfusion with high K+ solution and during exposure to tyramine. Moderate cooling reduced the activity of monoamine oxidase significantly more than that of COMT. The relative alterations in overflow of norepinephrine and its metabolites caused by a same degree of cooling in basal conditions and during the different forms of increased overflow of adrenergic transmitter suggest that lowering the temperature inhibits the exocytotic process, but at the same time slows down the diffusion of norepinephrine from the junctional cleft to the extracellular space to the extent that during sympathetic nerve stimulation at 24 degree C the effective junctional concentration of the transmitter may be comparable to that obtained at 37 degree C. The inhibitory effect of moderate cooling on the extraneuronal metabolism of norepinephrine appears to affect little the effective junctional concentration of the adrenergic transmitter.