Experimental studies on organic alkylnitrates have shown that both vasodilator potency and development of in vitro tolerance (tachyphylaxis) correlate with the number of nitrate groups in the molecule. However, introduction of an amino group to ethylnitrate yielded 2-nitrooxyethylammoniumnitrate (1), which is highly active but without inducing in vitro tolerance. Therefore, we prepared a series of aminoalkylnitrates and investigated vasorelaxation and tachyphylaxis on isolated prostaglandin F2α-precontracted porcine pulmonary arteries with intact endothelium. Tachyphylaxis was studied by incubating the arteries with EC100 of the respective aminoalkylnitrate and, after a 45-minute washout phase, measuring vasorelaxation again. All of the aminoalkylnitrates caused vasodilation, but the effect did not correlate with the number of nitrate moieties in the molecule. None of the substances was able to outperform compound 1, not even oligonitrates. Generally, structure-activity relationships found for alkylnitrates are obviously not valid for aminoalkylnitrates. Whereas the most potent aminomononitrate 1 evokes no in vitro tolerance, others exhibit tachyphylaxis independently of their vasodilator potency. We have shown that vasorelaxant activity and induction of tachyphylaxis are modulated significantly by introduction of an amino group to the alkylnitrate scaffold. Our results indicate that aminoalkylnitrates have to be considered as an individual class of nitrovasodilators with different structure-activity relationships and vasodilator properties.