Nitric oxide has emerged as one of the most important neurotransmitters mediating internal anal sphincter relaxation. The effect of glyceryl trinitrate, a nitric oxide donor, on anal tone was examined. Maximum resting pressure, predominantly a function of the smooth muscle internal anal sphincter, was measured before and 20 min after application of 0.2 per cent glyceryl trinitrate ointment in ten patients. Pressure decreased by a mean of 27 per cent (95 per cent confidence interval 18-36 per cent) (P = 0.0004) after administration of the drug. A further 20 patients were then randomized to either active or placebo ointment. Anal pressure was significantly decreased (P = 0.002) in those who received 0.2 per cent glyceryl trinitrate, but there was no significant reduction in the control patients. Mild headache occurred in two patients who were given the active preparation and in one who received placebo. Manometry was repeated 9h after application of glyceryl trinitrate and showed a sustained decrease in pressure in two patients. Topical glyceryl trinitrate may have a role in the treatment of anal fissure, haemorrhoids, certain types of constipation and anal pain. It may also reduce injury to the internal sphincter during peranal operations.