Objective: The aim was to determine the capacity of nodose ganglion afferent neurones with epicardial sensory endings to respond to mechanical and chemical stimuli, in particular to purinergic compounds. Methods: Alterations in spontaneous activity generated by epicardial afferent neurones in nodose ganglia in situ of 17 anaesthetised dogs were identified using extracellular recording techniques when mechanical and chemical stimuli were applied to their receptor fields, as well as during brief periods of coronary artery occlusion. Results: 92 cardiac afferent neurones were identified. Localised epicardial distortion modified the activity generated by 34 neurones [0.19(SEM 0.02) to 1.2(0.4) impulses.s(-1)]]. Application of bradykinin, substance P, N-6-cyclopentyl-adenosine or beta,gamma-methylene adenosine 5'-triphosphate to localised epicardial fields altered the activity of 69 neurones. Thus the majority of identified epicardial neurones responded to chemical stimuli alone (63%) as opposed to mechanical stimuli alone (25%), 12% responding to both types of stimuli. Activity was enhanced overall by chemical stimuli from a mean range of 0.1-0.4 to 11.6-13.2 impulses.s(-1). Following termination of short lasting chemical as opposed to mechanical stimuli, activity remained increased for up to 45 min. Activity generated by 16 chemosensitive neurones was modified by brief periods of coronary artery occlusion [0.26(0.12)-1.66(0.61) impulses.s(-1)]; activity increasing further [2.51(0.47) impulses.s(-)1] during reperfusion periods. Conclusions: (1) Chemical stimuli induce an order magnitude greater enhancement of activity generated by nodose ganglion cardiac afferent neurones than do mechanical stimuli, such enhancement persisting long after removal of chemical as opposed to mechanical stimuli. Thus qualitative and quantitative differences exists between central neuronal inputs derived from nodose ganglion epicardial afferent neurones sensitive to chemical as opposed to mechanical stimuli. (2) Adenosine and ATP can activate nodose ganglion cardiac afferent neurones.