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The tissue distribution of glyceryl trinitrate (GTN) and its two dinitrate metabolites 1,2-glyceryl dinitrate(1,2-GDN) and 1,3-glyceryl trinitrate (1,3-GDN), was studied in GTN-tolerant and nontolerant male Spra-gue-Dawley rats. The concentrations of GTh, 1,2-GDN, and 1,3-GDN were measured in plasma, heart, brain, liver, aortic tissue, and adipose tissue at various time points after a subcutaneous dose of GTh (50 mg/kg). At the first time point (5 hr), concentrations of GTN, 1,2-GDN, and 1,3-GDN in plasma were equal for tolerant and nonto-lerant rats, but the elimination rate was altered for the tolerant rats as compared with nontolerant rats. In adipose tissue, the concentra-don of GTh was significantly higher as compared with concentrations of the dinitrate metabolites. In contrast, the other tissues studied showed significantly higher concentrations of the GDNs when com-pared with GTh. The 1,3-GDN/1,2-GDN ratio decreased with time for both tolerant and nontolerant rats. This study indicates that long