Freshly prepared defibrinated serum rapidly releases the histamine content of rabbit platelets. The presence of calcium ion is required for this action. Releasing activity of the serum factor slowly declines on aging of the serum. Release is inhibited by heparin or by tosylarginine methyl ester, but not by soybean trypsin inhibitor. Release is also promoted by thrombin, which again is inhibited by heparin. The serum factor does not appear to be preformed thrombin since thrombin is effective in the absence of calcium ion. The findings suggest that the serum factor may be blood thromboplastin which acts directly on platelets or indirectly through the generation of thrombin.