We studied the actions of sandostatin (0.1-1000 nM), an analogue of somatostatin, on human atrial tissues obtained from hearts of 20 patients undergoing corrective cardiac surgery. In 3 preparations showing fast response action potential in normal [K]0 Tyrode solution, sandostatin induced little effect, even at the highest concentration (1 microM). In 10 preparations showing a slow rate of phase-0 depolarization when atrial fibers were depolarized (maximum diastolic potential near -40 mV) in high [K]0 (27 mM), sandostatin at concentrations as low as 1 nM decreased significantly the velocity of the upstroke, and the amplitude of slow response of the action potential as well as the force of contraction. In 6 experiments on spontaneously active atrial fibers (maximum diastolic potential = -53.8 +/- 2.7 mV), sandostatin increased the spontaneous cycle length in a fashion dependent upon concentration. The decrease in spontaneous rate of firing was associated with an inhibition of the late diastolic slope, a change also induced by somatostatin. A longer period of washout, however, (30 min or longer) was required for complete recovery from the depressant effects. Sandostatin (0.1-100 nM) also depressed triggered activity induced by cardiotonic agents. The present findings indicate that sandostatin induces a prolonged action in human atrial cells. Sandostatin may depress abnormal automatic rhythms through an inhibition of transmembrane influx of calcium.