Isosorbide-5-mononitrate (IS-5-MN) 5, 10, 20, 30, 40 and 50 mg were administered orally to 2 healthy male volunteers. The pharmacological effect was determined using digital pulse plethysmography and the orthostatic tilting test, and at the same time side effects were monitored. The threshold of oral activity of IS-5-MN was found to be 5 mg. The maximum response was reached with doses of 20–30 mg. The duration of action of this dose was approximately 8 h. Higher doses did not lead to any further increase, but rather to a decrease in the pharmacological response, while the side-effects, such as headaches, dizziness and nausea, became more prominent. In a randomized, double-blind, three-way cross-over study in 11 female volunteers IS-5-MN 30 mg proved to be more potent with respect to pharmacological activity than sustained released ISDN 20 mg (isosorbide dinitrate), whereas there was no difference in side-effects. Thus, it can be estimated that IS-5-MN 20 mg is approximately equivalent to 20 mg sustained released ISDN. IS-5-MN is rapidly absorbed after oral administration and the maximum concentration in serum was reached 1.2±0.2 h after doses of 10 to 50 mg. The pharmacokinetics showed dose-linearity. The compound was eliminated with an average half life of 4.04±0.16 h, which is appropriate for a reasonably prolonged duration of action without the need for a sustained release formulation.