Non-stochastic and stochastic 2D bilinear indices have been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. In order to evaluate the effectiveness of this novel approach in drug design we have modeled the angiotensin-converting enzyme inhibitory activity of perindoprilate's sigma-stereoisomers combinatorial library. Two linear discriminant analysis models, using non-stochastic and stochastic linear indices, were obtained. The models had shown an accuracy of 95.65% for the training set and 100% for the external prediction set. Next the prediction of the sigma-receptor antagonists of chiral 3-(3-hydroxyphenyl)piperidines by multiple linear regression analysis was carried out. Two statistically significant QSAR models were obtained when non-stochastic (R(2)=0.953 and s=0.238) and stochastic (R(2)=0.961 and s=0.219) 3D-chiral bilinear indices were used. These models showed adequate predictive power (assessed by the leave-one-out cross-validation experiment) yielding values of q(2)=0.935 (s(cv)=0.259) and q(2)=0.946 (s(cv)=0.235), respectively. Finally, the prediction of the corticosteroid-binding globulin binding affinity of steroids set was performed. The obtained results are rather similar to most of the 3D-QSAR approaches reported so far. The validation of this method was achieved by comparison with previous reports applied to the same data set. The non-stochastic and stochastic 3D-chiral linear indices appear to provide a very interesting alternative to other more common 3D-QSAR descriptors.