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We investigated the effects of intravenous regional injection of guanethidine and reserpine in a prospective, randomized, double-blind study of seven volunteers. The sympatholytic activities of these drugs were assessed separately for cholinergic and adrenergic function. Cold challenge was employed to magnify the effect on digital temperatures and alterations in pulse-volume. Only guanethidine significantly increased temperature (p less than 0.025) after cold challenge, this effect lasting for three days. No anticholinergic effect was found. Intravenous regional guanethidine may be useful in the treatment of vasospastic disorders and as prophylaxis for surgically treated patients in whom this complication may be expected to occur.