Nine healthy volunteers were studied with echocardiography and systolic time intervals before and after administration of 1 mg digoxin intravenously at supine rest and during 3-min isometric handgrip exercise. Eight of them were also studied following autonomic blockade, atropine (0.04 mg/kg), and propranolol (0.2 mg/kg) administered intravenously, otherwise the study program was the same. At rest, intravenous digoxin decreased the heart rate from 61 +/- 3 to 50 +/- 2 beats/min (p less than 0.001). Blood pressure, preload [defined as left ventricular end-diastolic diameter (LVEDD)] or afterload [estimated as left ventricular midsystolic circumferential wall stress (WS)], did not change. Fractional shortening increased from 29 +/- 2 to 33 +/- 2% (p less than 0.05), and the electromechanic systole time index (QS2i) decreased from 522 +/- 7 to 500 +/- 5 ms (p less than 0.01). The results indicate improved contractility due to digoxin. During handgrip, the heart rate decreased from 73 +/- 5 to 65 +/- 5 beats/min (p less than 0.01) as a result of digoxin. The LVEDD, WS or ejection phase indices, and systolic time intervals, did not change, suggesting that digoxin does not affect inotropy during isometric exercise. There was no changes in heart rate, preload or afterload, as a result of intravenous digoxin during autonomic blockade. Fractional shortening rose from 25 +/- 1 to 29 +/- 2 (p less than 0.05) and QS2i fell from 561 +/- 3 to 533 +/- 4 ms (p less than 0.001). The results indicate increased inotropy.(ABSTRACT TRUNCATED AT 250 WORDS)