To build a three dimensional structure model that correlates the biological activities and the structures of a series of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta-[1,2-]pyridin-11-yl) piperazines farnesyl protein transferase (FPTase) inhibitors.Mutation in the ras oncogene takes place in many human cancers, involving 30%-50% of colon and 90% of pancreatic cancer. Ras proteins function as central switches for signals given by growth factors that direct cell growth and cell differentiation. The dependence of the transforming activity of Ras on the farnesylation has led to intense search for FPTase inhibitors that may have therapeutic pontetial as anticancer agents. This paper is to build a three dimensional structural model that correlates the biological activities and the structures of a series of FPTase inhibitors. The investigated sixty-nine inhibitors contain six types of structures, the optimal conformations of which were studied using system search. A three dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed using the method of comparative molecular field analysis (CoMFA). The resulting cross-validation R2 is 0.581, non-cross-validation R2 0.968, SE 0.148, F 198.7. The predicted activities of 10 inhibitors using this 3D-QSAR model are comparable to the experimental activities, indicating that the 3D-QSAR model has ability to predict activities of new inhibitors and offers an approach to design new FPTase inhibitors.The information of CoMFA model offers an approach to designing new FPTase inhibitors.