We report the development of homology models of dopamine (D(2), D(3), and D(4)), serotonin (5-HT(1B), 5-HT(2A), 5-HT(2B), and 5-HT(2C)), histamine (H(1)), and muscarinic (M(1)) receptors, based on the high-resolution structure of the beta(2)-adrenergic receptor. The homology models were built and refined using Prime. We have addressed the required modeling of extracellular loop 2, which is often implicated in ligand binding. The orthosteric sites of the models were optimized using induced fit docking, to allow for side-chain flexibility, and the resulting receptor models have been evaluated using protein validation tools. Of the nine homology models developed, six models showed moderate to good enrichment in virtual screening experiments (5-HT(2A), 5-HT(1B), D(2), 5-HT(2C), D(3), and M(1)). The 5-HT(2A) receptor displayed the highest enrichment in virtual screening experiments with enrichment factors of 6.1, 6.9, and 5.9 at 2, 5, and 10%, respectively, of the screened database. However, three of the models require further refinement (5-HT(2B), D(4), and H(1)), due to difficulties in modeling some of the binding site residues as well as the extracellular loop 2. Our effort also aims to supplement the limited number of tested G protein-coupled receptor homology models based on the beta(2) crystal structure that are freely available to the research community.