Cold-induced platelet aggregation (CIPA) in PRP has previously been documented in connection with platelet preservation (4-15°C). This report describes hypothermia-induced platelet aggregation (HIPA) in whole blood and at temperatures used in open-heart surgery (24-32°C). HIPA (specifically, the formation of occlusive aggregates) was studied in human whole blood. Fresh heparinized (1.5 U/mi) human blood was cooled and maintained at target temperatures (15, 20, 24, 28, 32, or 37°C) as it flowed (1 ml/min) through 75-cm long 1/32?? internal diameter polymer conduit. The formation of aggregates in the tubing was verified using optical video microscopy and was quantified by a light-scattering method and a constant-pressure filtration method. Donors were tested at least twice at each target temperature and were classified into three separate response regimes (Low, Medium, and High) on the basis of the number of aggregates and the duration of their appearance. The screening of 121 donors (average age 22.3 ± 4.3 years) for HIPA at 24°C (the temperature of maximum response) indicated 14% High Responders, 18% Medium Responders, and 68% Low Responders. HIPA was inhibited by EDTA, citrate, PGE1, and Tirofiban, but not by aspirin, and it was enhanced by elevated heparin levels. HIPA was consistently noted in the blood of a subpopulation of donors, and the associated platelet aggregates in the blood of High Responders were rigid and occlusive. It is postulated that such aggregates may contribute to cognitive dysfunction noted in patients undergoing hypothermic open-heart surgery, and that postulus is being investigated. Am. J. Hematol. 69:45-55, 2002.