To determine whether intrinsic cardiac neurons involved in cardiac regulation possess neurokinin (NK) receptor subtypes, we administered selective NK receptor agonists individually (100 µM; 0.1 ml) into the coronary arterial blood supply of right atrial intrinsic cardiac neurons of 18 anesthetized dogs. The selective NK₁ receptor agonist [Sar⁹,Met(O₂)¹¹]-substance P depressed the spontaneous activity of right atrial neurons (26.7 ± 6.7 to 13.0 ± 4.0 impulses/min; P < 0.05) in 11 dogs and augmented such activity in the other 5 dogs (8.0 ± 3.1 to 27.8 ± 8.7 impulses/min; P < 0.05). Local administration of the selective NK₂ receptor agonist [-Ala⁸]-NKA-(410) depressed right atrial neuronal activity (27.3 ± 6.4 to 14.7 ± 3.8 impulses/min; P < 0.05), whereas the selective NK₃ receptor agonist senktide augmented such activity (18.9 ± 6.4 to 53.1 ± 12.0 impulses/min; P < 0.05). Left ventricular chamber pressure fell when selective NK₁ and NK₂ receptor agonists were administered. Increases in heart rate and right ventricular intramyocardial systolic pressure occurred when the selective NK₃ receptor agonist was studied. Administration of a selective NK₁ or NK₂ receptor antagonist altered neuronal activity, with no subsequent change in activity occurring after administration of its respective receptor agonist. Receptor autoradiography demonstrated tachykinin receptors associated with ventral right atrial intrinsic cardiac neurons. It is concluded that intrinsic cardiac neurons involved in cardiac regulation possess NK₁, NK₂, and NK₃ receptors and that some intrinsic cardiac neurons receive tonic input via endogenously released NKs.