The relaxation responses to adenosine and its analog inosine were compared in isolated canine coronary arterial rings (1-2 mm o.d.). The rings were contracted with prostaglandin F2 alpha (PGF2 alpha) and relaxed by progressively increasing the nucleoside concentration in the bathing medium. The maximal relaxation (Rmax) was expressed as a percentage of the increase in isometric tension caused by PGF2 alpha. All 15 rings responded to inosine, but only 10 responded to adenosine. In the 10 rings responding to both nucleosides, the ED50 (geometric mean with 95% confidence limits) for adenosine and inosine was 0.89 (0.76-1.26) and 224 (166-302) microM, respectively (p less than 0.001). However, in these 10 rings, the Rmax for adenosine was much less than that for inosine (p less than 0.05); thus, the mean ratio of adenosine Rmax/inosine Rmax was only 0.56 +/- 0.15 (SE). In further experiments, the methylxanthine aminophylline completely abolished the relaxation response to adenosine but did not affect the response to inosine. These results suggested that inosine relaxes the coronary artery by stimulation of a site distinct from the vascular adenosine receptor.