BACKGROUND No simple and reliable method of identifying patients with cobalamin malabsorption is available at present. The measurement of plasma holotranscobalamin, i.e. the metabolically active cobalamins bound to the transport protein transcobalamin, has been suggested as a means of fulfilling such criteria. DESIGN We describe a method that directly quantifies cobalamins attached to transcobalamin. The method is evaluated in patients referred for gastrointestinal examination because of suspected cobalamin malabsorption. RESULTS Of the 101 patients referred, all 48 with gastrointestinal conditions compatible with cobalamin malabsorption had plasma holotranscobalamin below 35 pmol L-1 (interval of 35-160pmol L-1). None of the patients with plasma holotranscobalamin above the lower reference limit had conditions compatible with cobalamin malabsorption. CONCLUSION The values obtained for plasma holotranscobalamin showed a better correlation with possible malabsorption than the values obtained for plasma cobalamins. The specificity of the test, however, needs to be elucidated further.