Both misoprostol (synthetic PGE1 analog) and De-Nol (factor releasing endogenous prostaglandins in the gastric mucosa) can be useful in the treatment of patients with gastric ulcer resistant to cimetidine according to their gastroprotective properties. 64 patients whose gastric ulcer had not healed after 6 weeks of therapy with cimetidine in daily dose of 1000 mg were treated in a comparative short-term trial to assess the relative efficacy of misoprostol (Cytotec; Searle) in daily dose of 800 micrograms (I group; n = 32) and colloidal bismuth subcitrate (De-Nol; Gist-Brocades), four times a day in dose of 5 ml diluted with 15 ml of water (II group; n = 32). Both groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion, ulcer size and localization in the stomach. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. Healing rates after 2 weeks of therapy appeared to be 47% for misoprostol and 34% for De-Nol. After 4 weeks of therapy the healing rates were 72% with misoprostol and 63% with De-Nol. No statistically significant differences in the therapeutic efficacy were observed between two groups of the patients. No correlation was found between the ulcer healing rates and size of ulcer, its localization or smoking habits. The moderate side effects (transient diarrhea) were observed in 22% of patients treated with misoprostol. These findings suggest that misoprostol is as effective as De-Nol in the treatment of gastric ulcers resistant to cimetidine.