To determine the effect of myocardial shortening velocity on the duration of electrical and mechanical systole, five healthy men, ages 32 to 41, were studied. Carotid message and atropine were used to define the effects of changes in heart rate without changes in shortening rate. The effects of amyl nitrite, which produced approximately the same degree of tachycardia as atropine but a significantly higher maximum shortening rate, were compared with those of atropine to assess the effects of faster shortening velocities. The increased heart rate produced by both agents caused a substantial decrease in both the QT and the S1S2 intervals, but the QT interval was longer and the S1S2 interval shorter with the amyl nitrite. Thus, the S2T interval was substantially longer after amyl nitrite. The results are in keeping with the finding in isolated cardiac muscle that active shortening increases action potential duration and decreases the duration of mechanical activation. These observations raise the possibility that longer QT intervals and shorter S1S2 intervals would also be seen in patients with hypokinetic ventricular segments when the healthy muscle contracts more vigorously to compensate for the weaker segments.