The pharmacological nature of purinoceptors in the rabbit coronary artery was investigated by comparing the extent of vasorelaxation induced by various purine derivatives, with or without amino group at C6 and with or without ribose at N9 in the purine structure. These derivatives were grouped according to structure--adenosine, inosine, adenine, and hypoxanthine analogs. The vasorelaxations produced by adenosine analogs were inhibited by aminophylline, while relaxations produced by the other three groups were unaffected. In the case of adenosine analogs, modification of amino group at C6 to secondary amine resulted in reduction of the potency of the vasorelaxing effect. The order of potency was as follows: adenosine greater than N6-(L)-phenylisopropyladenosine greater than N6-(D)-phenylisopropyladenosine greater than N6-cyclohexyl-adenosine greater than N6-(2,5-dioxo-3-pyrrolidinyl)-adenosine greater than kinetine riboside greater than N6-methyladenosine. On the other hand, the aminophylline-resistant relaxations of adenine analogs were augmented by modification of amino group at C6 to secondary or to tertiary amine. The order of potency was as follows: 6-cyclohexylaminopurine greater than 6-dimethylaminopurine greater than kinetine greater than 6-methylaminopurine adenine. Of adenosine, N6-cyclohexyladenosine, adenine, C6-cyclohexylaminopurine, and inosine, N6-cyclohexylaminopurine was the most potent phosphodiesterase inhibitor of crude enzyme prepared from rabbit aorta. From the order of potency of relaxations produced by adenosine analogs, adenosine receptors in the rabbit coronary artery seem to be of the A2-subtype. The relaxation induced by aminophylline-resistant adenine analogs may be due to activation of an unknown but specific site, since there is a structure-activity relationship in the relaxations produced by this group. Such relaxations may be linked to inhibition of phosphodiesterase in the rabbit coronary artery.