A new technique, the area method, is derived for the determination of partition coefficients for both blood-flow limited and membrane limited physiological pharmacokinetic models. This method was compared to a standard technique by Monte Carlo simulation. Partition coefficients were calculated for the blood-flow limited case for both eliminating and noneliminating organs. It was found that the area method compared favorably to a standard technique and was less prone to error. This may be attributed to the more subjective interpretation as to which data points are included in the terminal phase, since the standard method relies on the accurate determination of the terminal slope for the calculation of partition coefficients. Both methods are satisfactory for the calculation of partition coefficients with the area method being more accurate and precise.