Multiple tracer outflow dilution studies were performed on the normal canine tibia. In all cases 125I-labeled albumin was used as a vascular tracer. In one series of experiments 99mTc-labeled methylene diphosphonate and [14C]sucrose were used as test tracers, and in a second series 85Sr and 22Na were used. A bolus of three tracers was injected into the tibial nutrient artery, and fractional concentrations appearing in the ipsilateral femoral vein were measured for a period of 5 min. A distributed model, containing parameters for capillary and bone permeability and apparent volumes of distribution of interstitial fluid, was fitted to these data. It was found that there was no discrimination between movement of 85Sr or 22Na from interstitial fluid space into bone. Transcapillary exchange does not appear to be a significant barrier to exchange between blood and bone surfaces.