Alfentanil causes cardiac stimulation or depression in intact animals and in clinical practice; there is no information concerning its direct effects on the heart. Therefore, we studied the effects of alfentanil on isolated cardiac tissues from young adult rabbits. The right atrium with sinoatrial node (SA node) was beating spontaneously, and the left atrium and papillary muscle were stimulated. Isometric contraction was monitored. Alfentanil, in concentrations of 0.05-0.5 mM, decreased by 6%-55% the frequency of contractions of the right atrial-SA node in a dose-related manner. In left atria and right atrial-SA node, but not in papillary muscle, alfentanil in concentrations greater than or equal to 0.01 mM increased the peak developed force and its maximum rate of increase. The time-to-peak developed force was prolonged in papillary muscle but not in right atrial-SA node and left atria. The maximum rate of fall of peak developed force was increased in left atria and decreased in papillary muscle by the administration of alfentanil. The time-to-50% relaxation of peak developed force was not consistently affected by alfentanil in all three muscle preparations. The same concentrations of alfentanil (greater than or equal to 0.01 mM) increased resting force in papillary muscle but not in left atria or right atrial-SA node. It is concluded that alfentanil has direct positive inotropic and negative chronotropic effects on the heart and that it causes contracture of ventricular myocardium.