To study the interaction of butylated hydroxyanisole with various body tissues, a fully automated dynamic method was developed for the determination of plasma protein binding constants at 37 degrees, using membrane filtration equipment designed for dissolution rate studies. Appropriate equations were derived for the calculation of the free drug concentration from comparative diffusion rates across sealed dialysis sacs. A monoexponential equation described the diffusion in the absence of proteins, and a biexponential equation was fitted to diffusion from the drug-protein complex. The Scatchard and double-reciprocal plots were developed for butylated hydroxyanisole. A high degree of reproducibility was obtained for the calculation of protein binding constants (K = 2.4 - 2.9 X 10(4) and n = 1.4 - 1.32). The magnitude of these binding-constants suggests that any change in protein binding can have a significant effect on the distribution of butylated hydroxyanisole throughout the body, such as may be brought about by the common variations in the amount ingested.