A new approach for predicting the lipophilicity (log P), solubility (log Sw), and oral absorption of drugs in humans (FA) is described. It is based on structural and physicochemical similarity and is realized in the software program SLIPPER-2001. Calculated and experimental values of log P, log Sw, and FA for 42 drugs were used to demonstrate the predictive power of the program. Reliable results were obtained for simple compounds, for complex chemicals, and for drugs. Thus, the principle of "similar compounds display similar properties" together with estimating incremental changes in properties by using differences in physicochemical parameters results in "structure - property " predictive models even in the absence of a precise understanding of the mechanisms involved.