Soluble, truncated form of GPVI accumulates in the plasma of mice when human platelets circulate in the presence of anti-GPVI Fab fragments. NOD/SCID mice injected with human platelet concentrates along with Fab fragments directed against human GPVI (6B12) or PECAM-1 (1.3) were examined for the presence of soluble GPVI accumulation in the plasma. Streptavidin-Sepharose beads coated with a biotinylated form of the anti–human GPVI mAb, 11A12, were used to immunoprecipitate GPVI from human platelet lysates (HPL) or mouse plasma obtained from mice injected with human platelets and 6B12 or 1.3 fragments. On acid elution, samples were separated by SDS PAGE, transferred to a PVDF membrane, and probed for human GPVI using the mAb 6B12, which recognizes an epitope on the extracellular portion of human GPVI (A) or a rabbit polyclonal antibody directed against the cytoplasmic domain of GPVI (B). These data illustrate that a GPVI fragment corresponding to the extracellular domain accumulates in mouse plasma when human platelets circulate in the presence of an anti-GPVI Fab fragment of mAb 6B12.