The affinity of the classical β(2) adrenoceptor-selective inverse agonist ICI118,551 is notoriously lower for porcine β(2) adrenoceptors (p(2)βAR) than for human β(2) adrenoceptors (hβ(2)AR) but molecular mechanisms for this difference are still unclear. Homology 3-D models of pβ(2)AR can be useful in predicting similarities and differences, which might in turn increase the comparative understanding of ligand interactions with the hβ(2)AR. In this work, the pβ(2)AR amino acid sequence was used to carry out homology modeling. The selected pβ(2)AR 3-D structure was structurally and energetically optimized and used as a model for further theoretical study. The homology model of pβ(2)AR has a 3-D structure very similar to the crystal structures of recently studied hβ(2)AR. This was also corroborated by sequence identity, RMSD, Ramachandran map, TM-score and docking results. Upon performing molecular docking simulations with the AutoDock4.0.1 program on pβ(2)AR, it was found that a set of well-known β(2)AR ligands reach two distinct binding sites on pβ(2)AR. Whereas one of these sites is similar to that reported on the hβ(2)AR crystal structure, the other can explain some important experimental observations. Additionally, the theoretical affinity estimated for ICI118,551 closely agrees with affinities estimated from experimental in vitro data. The experimental differences between the human/porcine β(2)ARs in relation to ligand affinity can in part be elucidated by observations in this molecular modeling study.