A CoMFA analysis of eight compounds related to disoxaril whose X-ray structures bound to HRV-14 had been determined resulted in a strong positive correlation of activity with steric effects of the compounds, particularly toward the pore end of the compound binding site, and no correlation with electrostatic effects. These results confirm what had been previously found, that the activity of these compounds was highly dependent upon their hydrophobic nature as expressed by log p. The CoMFA study also confirmed the results from the comparison of a series of active and inactive compounds using volume maps which showed that bulk at the pore end of the molecule was conducive to high levels of antiviral activity while excessive bulk around the ring led to poor activity.