A Biopharmaceutics Drug Disposition Classification System (BDDCS) was proposed to serve as a basis for predicting the importance of transporters in determining drug bioavailability and disposition. BDDCS may be useful in predicting: routes of drug elimination; efflux and absorptive transporters effects on oral absorption; when transporter-enzyme interplay will yield clinically significant effects (e.g. low drug bioavailability and drug-drug interactions); and transporter effects on post-absorptive systemic drug levels following oral and i.v. dosing. For highly soluble, highly permeable Class 1 compounds, metabolism is the major route of elimination and transporter effects on drug bioavailability and hepatic disposition are negligible. In contrast for the poorly permeable Class 3 and 4 compounds, metabolism only plays a minor role in drug elimination. Uptake transporters are major determinants of drug bioavailability for these poorly permeable drugs and both uptake and efflux transporters could be important for drug elimination. Highly permeable, poorly soluble, extensively metabolized Class 2 compounds present the most complicated relationship in defining the impact of transporters due to a marked transporter-enzyme interplay. Uptake transporters are unimportant for Class 2 drug bioavailability, (ensure space after,) but can play a major role in hepatic and renal elimination. Efflux transporters have major effects on drug bioavailability, absorption, metabolism and elimination of Class 2 drugs. It is difficult to accurately characterize drugs in terms of the high permeability criteria, i.e. > or =90% absorbed. We suggest that extensive metabolism may substitute for the high permeability characteristic, and that BDDCS using elimination criteria may provide predictability in characterizing drug disposition profiles for all classes of compounds.