The mechanism and rates of drug transport through capillaries, interstitial space and cells will be measured using an excised perfused rat diaphragm as a model tissue. Effects of physical chemical properties of drugs (size, lipophillic nature, protein binding) will be correlated with transport rates. The interaction of fluid exchange in the microcirculation on drug transport will be evaluated. Diffusion rates, radio-autography of muscle sections, and histological information will be combined to develop a structured mathematical-model of the microcirculation. The results should be useful in developing pharmacokinetic strategies in disease states where microcirculation plays an important role in drug transport to target cells, e.g. tumors.