Incubation of A type prostaglandins with whole blood or washed red cells at 37 degrees C converted them to more polar products with negligible vasodepressor and smooth muscle-contracting activities. This conversion did not occur in platelet-rich plasma. Uptake of the prostaglandins by red cells was demonstrated at both 4 degrees C and 37 degrees C. The data suggest 1) that if PGA is released from tissues into the blood stream or is administered for therapeutic purposes, its biological activity would be diminished by human red cells, and 2) that development of an assay for PGA in blood should take into account its uptake and metabolism by human red cells.