An oral dose of 20 mg sustained release glyceryl trinitrate (GTN, Nitro Mack Retard) was administered to 6 healthy human subjects. In the plasma of all subjects the metabolically generated glyceryl nitrates glyceryl 1,2-dinitrate (G-1,2-DN), glyceryl 1,3-dinitrate (G-1,3-DN), glyceryl 2-nitrate (G-2-N) and glyceryl (G-1-N) could be identified, but no intact GTN was found. The nitrate metabolites showed sustained plasma profiles which can be explained by a slow release of GTN with subsequent complete first-pass denitration. The plasma concentrations of the mononitrates were generally higher than those of the dinitrates. G-1,2-DN and G-2-N, the metabolites which contain a nitrate group in the central position, showed higher concentrations than the respective isomeric compounds. The combined glyceryl dinitrates reached concentrations between 10.2 and 21.7 ng/ml, the combined mononitrates varied from 70.4 to 106.8 ng/ml. The ratios of the areas under the curve G-1,3-DN:G-1,2-DN:G-1-N:G-2-N were 1:4:19:64, on average. Taking into consideration the relative vasodilator potencies of glyceryl nitrates in the animal, our results give rise to the hypothesis that the glyceryl dinitrate metabolites participate in the clinical efficacy of large oral doses of sustained release GTN.