Molecular modeling techniques were used to build a three-dimensional model of the rat 5-HT 2 C receptor, which was used to examine receptor interactions for protonated forms of serotonin, ketanserin and ritanserin. Molecular dynamics simulations which were started with the fluoro benzene moiety of ketanserin and ritanserin oriented towards the cytoplasmic side of the receptor model, produced the strongest antagonist-receptor interactions. The fluoro benzene ring(s) of the antagonists interacted strongly with aromatic residues in the receptor model, which predicts slightly different orientations and ligand-receptor interactions of ketanserin and ritanserin at a putative binding site. The model suggests that Asn 3 3 3 (transmembrane helix 6) is involved in a hydrogen-bonding interaction with ketanserin, but not with ritanserin. The model also also suggests that the position corresponding to Cys 3 6 2 (transmembrane helix 7) may be an important determinant for specifying 5-HT 2 A receptor selectivity in ketanserin binding.