A multicenter study was conducted on 173 patients with active, endoscopically proven duodenal ulcers (158 men, 15 women). They were randomly assigned, in a double-blind manner, to two groups: those receiving placebo capsules (91 patients) and those receiving capsules containing 100 microgram of 15(R)-15-methyl prostaglandin E2 (arbaprostil) (82 patients). Each drug was ingested four times a day (1 h before meals and at bedtime) for 28 days. Endoscopy was performed on days 0, 14, and 28 after the trial began. At each examination, the ulcer size was measured and whether the ulcer had healed was recorded. Arbaprostil increased the incidence of ulcer healing to approximately the same degree as reported in most extensive studies with cimetidine. At 14 days, three times as many patients were totally healed in the arbaprostil-treated as in the placebo-treated group (37% vs. 12%, p less than 0.001). At 28 days, 67% of patients receiving arbaprostil were healed compared with 39% in the group receiving placebo (p less than 0.001). Similarly, the ulcer size, measured endoscopically, was much smaller after arbaprostil administration than in the group receiving placebo after both 14 and 28 days (p less than 0.001). Side effects attributable to treatment consisted primarily of loose stools and diarrhea (34%). Smoking retarded healing in the placebo-treated group (p less than 0.05), but did not significantly retard healing in patients treated with arbaprostil. We conclude that arbaprostil markedly accelerates the healing rate of active duodenal ulcers. This effect may be due to inhibition of acid secretion as well as gastric cytoprotection.