A three-dimensional model of the amino terminal domain (ATD) of the mGluR1 receptor subtype was constructed on the basis of the previously reported sequence homology with bacterial periplasmic proteins. The model was utilized for revealing structural motifs affecting the interaction with mGluR1 agonists and competitive antagonists. The agonist binding site region, identified on the basis of published site-directed mutagenesis experiments, is located on the surface of one of the two lobes constituting the mGluR1 ATD. A number of electrostatic and hydrogen-bonding interactions can be detected between mGluR1 agonists such as L-Glu (1), Quis (2), and (1S,3R)-ACPD (4) and binding site residues. A different binding mode was proposed for mGluR1 competitive antagonists such as 4CPG (5), 4C3HPG (6), and UPF523 (10). Interactions with both lobes of the ATD of mGluR1 and the lack of a specific role for the phenyl moiety of mGluR1 antagonists are important features of the proposed antagonist binding mode. The correspondence of the molecular modeling results with the pharmacological data of mGluR1 agonists and competitive antagonists is a confirmation of the plausibility of the model.