Experiments were performed to determine whether depression of venomotor responses with halothane results from interference with sympathetic activation or from an effect on venous smooth muscle cells. Changes in isometric tension of isolated canine saphenous-vein strips were recorded. Adrenergic activation was achieved by transmural electrical stimulation, by addition of tyramine, and by addition of morepinephrine. Halothane (0.5 to 3 per cent) did not significantly alter basal tension. It lessened the reaction of the veins to electrical stimulation but not their response to norepinephrine; it increased the response to tyramine. Since the responses to norepinephrine and tyramine were not decreased, halothane appears to act on the nerve terminal to prevent release of neurotransmitter associated with nerve-terminal depolarization. Thus, halothane causes inhibition of electrically induced venoconstriction in cutaneous veins, probably by interfering with the release of norepinephrine from nerve terminals rather than by an inhibitory effect on the smooth muscle cells.