Intravenous infusions of nitroglycerin (GTN), 1,2-glyceryl dinitrate (1,2-GDN), and 1,3-glyceryl dinitrate (1,3-GDN) were given to four conscious dogs at 10 micrograms/min, 30 micrograms/min, 50 micrograms/min, and 70 micrograms/min of GTN and 20 micrograms/min and 100 micrograms/min of GDNs. The steady state plasma concentrations (Css) of GTN were reached after about 60 min whereas for 1,2-GDN and 1,3-GDN the Css were reached at about 150 min after the infusion began. Except for one dog, the Css of GTN were not proportional to infusion rate, however, all dogs together showed a good linear relationship between Css of GTN and infusion rates with an average correlation coefficient of 0.917 +/- 0.102. Large variability in GTN clearance after various infusion rates was observed in all dogs. The Css ratios of 1,2-GDN/GTN and 1,3-GDN/GTN yield overall averages of 31.5 +/- 17.2 and 5.47 +/- 3.19, respectively. Average Css ratios of metabolites 1,2-GDN/1,3-GDN were 5.78 +/- 1.23. This ratio is different from those obtained after iv bolus and oral dosing indicating that the biotransformation of GTN to 1,2-GDN and 1,3-GDN differs for each dosing route. The clearances for 1,2-GDN and 1,3-GDN were not changed over the dose range of 20 micrograms/min to 100 micrograms/min. Terminal half-lives of 1,2-GDN and 1,3-GDN postinfusion were similar to those values obtained after a single bolus dose (45 min). It appears that all the GTN dose at steady state can be accounted for by the formation of measurable 1,2-GDN and 1,3-GDN. Large intra- and interdog variations in systolic blood pressure decrease (SPD) following infusions of GTN were observed, however, all dogs showed a clear systolic blood pressure decrease when the highest infusion rate (70 micrograms/min) was given. No significant systolic blood pressure drop was detected following 20 micrograms/min infusions of 1,2-GDN or 1,3-GDN. It was clear that systolic blood pressure in all dogs decreased following 100 microgram/min infusions of 1,2-GDN or 1,3-GDN. When SPD values were plotted vs. log GTN concentrations following the infusion of 70 micrograms/min of GTN in all four dogs, a counterclockwise hysteresis was observed indicating the significant contribution of the active dinitrate metabolites to GTN pharmacodynamics.