The objective of this study was to predict absolute bioavailability in humans from animal data using interspecies scaling as well as indirect approaches. Five different methods were used to predict absolute bioavailability in humans: (i) absolute bioavailability vs body weight (allometric approach); (ii) F = CL(IV)/CL(oral); (iii) F = 1-[CL(IV)/Q]; (iv) F = 1-[CL(oral)/Q]; and (v) F = Q/[Q + CL(oral)]. Methods II-V are indirect approaches, where predicted i.v. or oral clearance and hepatic blood flow (Q) (1500 ml/min) were used to predict absolute bioavailability in humans. Fifteen drugs were tested and the results of this study indicate that all five approaches predict absolute bioavailability with different degrees of accuracy, and are therefore unreliable for the accurate prediction of absolute bioavailability in humans from animal data. In conclusion, although the above-mentioned approaches do not accurately predict absolute bioavailability, a rough estimate of absolute bioavailability is possible using these approaches.