Abstract: An assay for functional high molecular weight kininogen in plasma is provided. A plasma sample of unknown functional high molecular kininogen content is treated to inactivate plasma protease inhibitors and kallikrein, and is appropriately neutralized and diluted. Exogenous factor XIIa and factor XI are added to the sample to form a reaction mixture which is incubated with a contact-activating surface. The concentrations of factor XIIa and factor XI in the reaction mixture are selected such that the concentration of functional high molecular weight kininogen in the sample is rate-limiting in the HMWK-mediated activation of factor XI by factor XIIa. The amount of factor XIa generated in the sample, which under the conditions of the assay is directly proportional to the concentration of functional HMWK, may be determined by functional assay using an appropriate factor XIa substrate.