Pentaerythritol tetranitrate (PETN) has raised a great deal of interest in recent years, because it is probably the only organic "tolerance-sparing" nitrate. However, some clinicians doubt whether this drug is really effective in reducing angina and ischemia. The aim of this study, therefore, was to evaluate the clinical efficacy and adverse effects (AEs) of PETN in two doses: 50 mg (PETN-50) and 100 mg (PETN-100), after single ingestion. Twenty-five male patients (pts) with stable angina were enrolled in a randomized, double-blind and placebo (P) controlled study. Ten of them received PETN-50 or P and fifteen of them PETN-100 or P. Antianginal efficacy of the drugs was evaluated by analyzing the parameters of tolerance of effort and coronary reserve taken from serial exercise stress tests on the treadmill performed before single oral ingestion, then after 2h and 6h. Simple hemodynamic parameters were also evaluated at rest and during exercise. In comparison to P, PETN-50 did not change any parameter of tolerance of effort and coronary reserve, nor any simple hemodynamic parameter (all values statistically not significant - n.s.). However, in comparison to P, PETN-100 significantly improved the mean total walking time after 2h by 20.8% (p < 0.01) and also after 6h by 11.3% (p < 0.05). Similarly, PETN-100 improved walking time to angina after 2h by 18.8% (p < 0.05) and after 6h by 10.5% (p < 0.05). The drug also improved walking time to ischemia after 2h by 32.5% (p < 0.01) and after 6h by 13.8% (p < 0.05). PETN-100 did not significantly change the resting heart rate, but it decreased resting systolic blood pressure in both positions 6h after ingestion: in supine by 6.1% (p < 0.05) and in standing by 5.9% (p < 0.05). No postural hypotension in any pt occurred. Diastolic blood pressure significantly decreased only in standing position by 6.8% (p < 0.05) after 6h. During maximal exercise no significant reduction of systolic blood pressure occurred, but there was a significant reduction in diastolic blood pressure 6h after ingestion only. This study shows the good clinical tolerance and safety of PETN in both doses. There were no AEs after single ingestion of PETN-50 and AEs after ingestion of PETN-100 included headaches in 3 pts only (in 1 pt after P) in the group of 15 pts. Thus no clinical activity of PETN-50 was shown. However, our investigations suggest that PETN-100 is an active coronary drug, effective not less than 6 h after ingestion, and well tolerated by pts. Further studies are needed to evaluate the efficacy of PETN in long-term therapy.