Excellent clinical results have been reported with sclerotherapy for control of nonvariceal gastrointestinal hemorrhage. However, there are few controlled or comparative data on different sclerosing agents for treatment of lesions with active arterial bleeding or nonbleeding visible vessels. In a controlled, randomized study of canine small bowel arteries our purposes were (a) to evaluate the efficacy for arterial coagulation of six sclerosing agents compared with normal saline control, (b) to compare the resultant tissue injury of agents, and (c) to elucidate the possible mechanisms of arterial coagulation and tissue injury of the agents. The agents evaluated were (a) 98% ethanol, (b) TES, a mixture with final concentration of 1% tetradecyl sulfate, 32% ethanol, and 0.3 normal saline, (c) 1% polidocanol (Ethoxysclerol), (d) 1:10,000 epinephrine, (e) 7.2% hypertonic saline, (f) 3.6% hypertonic saline, and (g) 0.9% saline (normal saline control). Agents were injected from the mucosal side of the small bowel into and around the pentrating serosal arteries in the subserosal space. Ethanol and TES were the most effective agents for arterial coagulation. Polidocanol was less effective than ethanol and TES. However, it was the only other agent that induced significant arterial coagulation. Alcohol and TES also caused significant injury in surrounding tissue. The degree of this injury was dependent on the total volume injected. Epinephrine induced significant mucosal damage without significant serosal injury or arterial coagulation. The coagulation and tissue injury effects of hypertonic saline injections were not significantly different from normal saline control.