A pharmacokinetic model that incorporates linear binding of drug to plasma proteins and tissue indicates the same relationship between apparent volume of distribution and drug binding as that proposed by Gillette (1971) based on a simple distribution model. Apparent volume of distribution (V) is directly proportional to free fraction of drug in plasma (fp) and indirectly proportional to free fraction of drug in tissue (fT). In the case of a constant fT, a plot of V versus fp will be linear with an intercept equal to plasma volume (Vp). If fT changes with fp, an apparently linear plot may result but the intercept will exceed Vp. An approach to the calculation of fT, a composite binding parameter, is presented and illustrated by comparing the tissue binding of tolbutamide in patients during acute viral hepatitis and upon recovery.