Advances in the preparation of commercial Factor VIII concentrates have decreased the clinical use of cryoprecipitate to replace Factor VIII coagulant activity. Cryoprecipitate is now frequently transfused as a source of fibrinogen or von Willebrand factor (vWF). The minimum acceptable content of Factor VIII is prescribed, but no attempt is made to optimize, standardize, or assess the content of fibrinogen or vWF in cryo. If reasonably accurate information on the composition of cryoprecipitate were available, the physician could calculate an appropriate dose of cryo, thus avoiding unnecessary donor exposures and waste of product. This study was designed to measure the functionally active vWF and fibrinogen in cryoprecipitate prepared by three techniques in an attempt to optimize the yield of these hemostatically important components, and to obtain accurate information on the composition of the product. Cryoprecipitate was made from 82 units of fresh frozen plasma (FFP) as follows: (1) most of the supernatant plasma was expressed from "dry" cryo; (2) about 15 mL of plasma was left in each "regular" unit; and (3) "overnight" units were made from FFP thawed overnight in a refrigerator rather than in a 4 degrees C water bath as for the dry and regular units. Dry, regular, and overnight units had volumes of 8.8 +/- 1.5, 16.6 +/- 3.9, and 15.1 +/- 2.4 mL/bag, respectively. Dry cryoprecipitate units had significantly less fibrinogen and vWF than regular or overnight units. The vWF multimer pattern for all three types of cryoprecipitate was indistinguishable from that of normal pooled plasma. Thus, the amount of plasma expressed during preparation has a significant impact on the vWF and fibrinogen content of the resulting product. The amounts of these clinically important proteins should be assayed as a step toward rational determination of optimal cryoprecipitate doses in specific clinical settings.