Measurements were made of the concentration of dipyridamole in the plasma of man, dogs, pigs, and pigeons at different times after oral administration of the drug. In dogs and in man, there was considerable variation in the plasma levels of the drug in different subjects. Pigs and pigeons always had much lower levels of the drug in plasma than did men and dogs given comparable doses. After intravenous injection of dipyridamole to pigs, a large proportion of the drug appeared to leave the plasma almost immediately; subsequently, the half-life of the drug remaining in the plasma was quite similar to that previously reported in man. The administration of aspirin with dipyridamole sometimes resulted in higher blood levels of the drug in dogs, man, and pigs, but the effects were small. The wide variations in plasma drug levels observed indicate that in future human or experimental trials designed to evaluate the antithrombotic effect of dipyridamole, plasma levels of the drug should be routinely monitored.