We built a model for the 5-HT1A receptor, using the 3D-structure of bacteriorhodopsin as a structural template. With the use of site-directed mutagenesis data, several potent 5-HT1A agonists, belonging to five different structural classes, and an aryloxypropanolamine antagonist, were docked into the receptor model. After docking, the surrounding of the ligands appeared to be in full agreement with previously reported SAR-data of 5-HT1A ligands. In this study, for the first time, an explanation for 5-HT SAR results is given in terms of interactions between ligands and amino acid residues. Also the selectivity of 8-OH-DPAT for the 5-HT1A receptor is accounted for. In our model the agonists and the antagonist interact with different residues on several helices. They all interact with the essential aspartic acid on helix III, that is known to bind all amines to receptors for biogenic amines. This partial overlap of the binding sites accounts for the antagonism of the class of aryloxypropanolamines and for the deviating SAR of this class of compounds when compared to agonists.