Platelet-aggregating vWF activity in several animal species is difficult to detect with either the ristocetin co-factor test or the PAF test using human platelets, indicating considerable species restriction in applicability of these procedures. VCA, a recently described second "activator" of vWF, was found not to be restrictive as to species and readily elicited the vWF response in all 13 animal plasmas tested. For any one of the animal plasmas, the vWF-dependent platelet aggregation reaction can be demonstrated by using VCA with either homologous or heterologous species of platelets. VCA was employed with lyophilized platelets in two types of platelet aggregating test systems, a macroscopic procedure and an aggregometric method. Many of the animal plasmas (dog, rabbit, horse, cow, cat, sheep, and goat) had about three to five times the plasma vWF content of human plasma. Pig and rat plasmas had vWF levels approximating those of human plasma. Guinea pig plasma had about half as much vWF as human plasma. VCA also caused a well-defined vWF-dependent platelet response in PRPs. The data suggest considerable differences in the rate of aggregation of platelets from different species. Bioassay of vWF can be performed with the different animal plasmas if the source of platelets and the VCA concentration are controlled. VCA thus appears to provide a broad-spectrum probe for vWF and is effective in the various species combinations of plasma and platelets.