Hologram QSAR studies were conducted on a series of 60 training set of cannabinoid-1 receptor (CB(1)) antagonists. Significant cross-validated correlation coefficients (q(2)=0.763) and noncross-validated correlation coefficients (r(2)=0.897) were obtained. The model was then employed to predict the biological activities of 15 test set compounds, and a good agreement between the experimental and predicted values was verified exhibiting a powerful predictable capability of this model (q(pred)(2)=0.868). Contribution map shows that 1,2,4-trizole and cyclopropane moieties make big contributions for the activities. Both the HQSAR model and analysis from the contribution map should be useful for the further design of novel structurally related CB(1) antagonists.