BACKGROUND: Topical application of glyceryl trinitrate (GTN) ointment heals chronic anal fissures, providing an alternative to the traditional first line treatment of surgical sphincterotomy. AIMS: To determine the most effective dose of topical GTN for treatment of chronic anal fissures and to assess long term results. METHODS: Seventy consecutive patients with chronic anal fissure, were randomly allocated to eight weeks treatment with placebo, 0.2% GTN three times daily, or GTN starting at 0.2% with weekly 0.1% increments to a maximum of 0.6%, in a double blind study. RESULTS: After eight weeks fissure had healed in 67% of patients treated with GTN compared with 32% with placebo (p=0.008). No significant difference was seen between the two active treatments. Headaches were reported by 72% of patients on GTN compared with 27% on placebo (p<0.001). Maximum anal sphincter pressure reduced significantly from baseline by GTN treatment (p=0.02), but not placebo (p=0.8). Mean pain scores were lower after treatment with GTN compared with placebo (NS). Of fissures healed with placebo 43% recurred, compared with 33% of those healed with 0.2% GTN and 25% healed with escalating dose GTN (p=0.7). CONCLUSIONS: GTN is a good first line treatment for two thirds of patients with anal fissure. An escalating dose of GTN does not result in earlier healing. Significant recurrence of symptomatic fissures and a high incidence of headaches are limitations of the treatment.(Gut 1999;44:727-730)