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The effect of isometric handgrip exercise (IHG) on left ventricular (LV) size and performance was studied noninvasively on 15 normal subjects at rest and at the end of 3 min of IHG at 50% of maximum contraction. Left ventricular internal diameter was measured at end-diastole and end-systole on LV echograms, the indirect carotid pulse was recorded, and blood pressure measured by sphygmomanometry. Using the cube formula, LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were computed, and stroke (SI) and cardiac (CI) indices were derived. Mean blood pressure (BPm) and systemic vascular resistance (SVR) were calculated from these data by a technique previously described. In comparison to values at rest, IHG resulted in a significant ( P < 0.01) rise in CI (3.5 ± 0.2 to 4.4 ± 0.3 L/min/m 2 ), BPm (87 ± 2 to 120 ± 4 mm Hg) and heart rate (79 ± 3 to 97 ± 4 beats/min). The product (SI x BPm), used as an index of LV stroke work, increased substantially (52 ± 3 to 74 ± 4 gm-m/m 2 ). No significant change was noted in EDVI (60 ± 4 to 62 ± 3 ml/m 2 ), SI (44 ± 2 to 46 ± 2 ml/m 2 ), and SVR (1209 ± 69 to 1275 ± 63 dynes/sec/cm –5 ). Thus normal hearts responded to IHG by increasing CI through tachycardia and pumping the same SI against increased afterload, without utilizing diastolic volume reserves. These data support the hypothesis that isometric muscular exercise leads to an augmentation of LV myocardial contractility in normal man.