After more than centenary successful use of nitroglycerin in clinical practice, scientists revealed that its medicinal effect is based on release of potent vasodilator nitric oxide (NO). More-over, the experiments showed that NO plays an important role in hypoxia vasodilator mechanisms. Since nitroglycerin is an exogenous NO donor and moderate hypoxia facilitates release of endogenous NO, we suggested that nitroglycerin effects are changed in high altitude. To examine this suggestion, we have carried out a standard nitroglycerin test for healthy volunteers living in high and low altitude areas. Comparison of obtained results showed that the use of oral nitroglycerin in high altitude areas is accompanied with significant prolonged decrease in blood pressure and total vascular resistance. So, we first found that high altitude hypoxia strengthens and extends nitroglycerin-induced peripheral vasodilation in healthy subjects. This effect might be caused by additive vasodilator effect of nitroglycerin and moderate hypoxia. This data should be taken into account when prescribing exogenous and endogenous NO donors to treat patients in high altitude areas.