N6-substituted adenosine derivatives can be very potent and selective agonists at A1 receptors. The N6-region is usually described by a general model introduced by Kusachi et al. (J. Med. Chem. 1985, 28, 1636). Structure-activity relationships for this region have recently been reported from a detailed study by Daly et al. (Biochem. Pharmacol. 1986, 35, 2467). The N6-region of the A1 receptor was now investigated in further detail with the aid of computer graphics. A map of the N6-region was constructed on the basis of a selected set of data from Daly et al. This map allows Kusachi's model to be extended with two new subregions: a C subregion, accommodating cycloalkyl substituents and a B subregion, which is filled by bulky substituents, such as a norbornanyl moiety. Furthermore, three regions can be distinguished, where occupation leads to diminished receptor affinity, so-called forbidden areas. The extended model permits the contribution of each subregion to be determined quantitatively, allowing accurate prediction of affinities of compounds that were not used to construct the map.