This double-blind, randomized, multicenter study was designed to determine the short-term and long-term efficacy of intravenous regional block with guanethidine in patients with reflex sympathetic dystrophy (RSD)/causalgia. Sixty patients were enrolled to receive four intravenous regional blocks at 4-day intervals with either guanethidine or placebo in 0.5% lidocaine. Each patient was randomized to receive either one, two, or four blocks with guanethidine. Follow-up visits were scheduled for 4 days, 1 mo, 3 mo, and 6 mo after their final block. At 4 days after the initial block, the group treated with placebo experienced a greater decrease in pain scores than those treated with guanethidine, although this difference was not statistically significant. On long-term followup there was no difference in pain scores between groups receiving one, two, or four guanethidine blocks. Overall, only 35% of patients experienced clinically significant relief on long-term followup even though all were treated early in the evolution of RSD.