Using platelet-rich plasma freshly obtained by plasmapheresis, the spread areas of human platelets settled onto substrata of different surface energies were measured to evaluate the hypothesis that initial platelet spreading response is surface dependent. At 37 degrees C, minimal platelet spread areas were found on substrata with critical surface tension between 20 and 30 mN/m (dynes/cm), and increased spreading and morphologic changes occurred on substrata of both higher and lower critical surface tension. This differential response was absent at 25 degrees C. Therefore, measurement of spread platelet area at physiologic temperature rather than number of attached cells is proposed as a superior method of estimating apparent blood compatibility of new biomaterials.