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OBJECTIVE—To assess the diagnostic value and safety of sublingual glyceryl trinitrate tilt testing compared with isoprenaline infusion in patients with unexplained syncope. DESIGN—Glyceryl trinitrate and isoprenaline tilt tests were performed in two successive days on a random basis in cases and controls. SETTING—Outpatient cases with syncope referred to Shahid Rajaii Heart Hospital. SUBJECTS—65 consecutive patients with unexplained syncope after thorough work up; 20 healthy volunteers. RESULTS—Positive responses were observed in 20 patients during the passive phase. Of the other 45 patients, positive responses occurred in 25 cases during the glyceryl trinitrate phase and in 26 cases during the isoprenaline phase. In the control group, positive responses during the passive, glyceryl trinitrate, and isoprenaline phases occurred in one, one, and two cases, respectively. The sensitivity and specificity of the protocols were 55% and 94.7%, respectively, for glyceryl trinitrate v 58% and 89.4% for isoprenaline. Owing to discordant responses in 75% of the cases, the sequential use of the tests (if one was negative) would increase the sensitivity to 84% while decreasing the specificity slightly (to 84%). Side effects were less frequent with glyceryl trinitrate. CONCLUSIONS—Sublingual glyceryl trinitrate tilt testing is an effective and safe alternative to the isoprenaline infusion test and can be used as a complementary test. Keywords: syncope; tilt table test; isoprenaline; glyceryl trinitrate