A randomized, double-blind, crossover study comparing the efficacy of intra-arterially administered reserpine with physiological saline was undertaken in 12 patients with progressive systemic sclerosis and four with overlap syndromes with predominant features of scleroderma. Patients were treated for either refractory digital ulcers or severe, incapacitating Raynaud phenomenon. Ten of 16 patients showed improvement with the injections. Favorable responses occurred in 12 of 26 patients given placebo injections and 12 of 25 patients given reserpine injections. No difference in efficacy between intra-arterial administration of reserpine and saline could be ascertained.