1. As the majority of drug molecules are relatively small and lipophilic, capillary uptake in those regions with a continuous endothelium, such as the heart, has generally been regarded as taking place by flow-limited transcellular capillary transport. Little attention has been paid to myocardial paracellular capillary transport of hydrophilic drugs, despite efficient transport of hydrophilic solutes, such as sucrose, inulin and EDTA, by this route. 2. The paracellular pathway is formed by the cleft between adjacent endothelial cells and its permeability properties are determined by the tight junction, a region of restricted diameter within the cleft. Paracellular capillary permeability is modulated by circulating macromolecules, such as albumin, by an unknown mechanism thought to involve the intra-endothelial cell Ca2+ concentration. 3. Studies in perfused rat heart have shown that capillary permeability of quinidine does not vary when perfusate pH is varied from 7.0-8.0, suggesting that capillary transport involves the ionized as well as unionized moiety. Addition of albumin to the perfusion medium reduced quinidine capillary permeability, which is consistent with paracellular transport of quinidine ions. 4. Paracellular transport increases in capillary inflammation. Therefore, if there is significant paracellular transport of hydrophilic drugs, an increase in uptake of such drugs in areas of inflamed myocardium associated with acute myocardial infarction would be expected to result.