PurposeAccurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast‐enhanced MR angiography (CE‐MRA). This study measured the longitudinal relaxation rate constants (R1) over a concentration range for non‐protein‐binding and protein‐binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.MethodsRelaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE‐MRA.ResultsIn plasma, the 1H2O R1 [CR]‐dependence was nonlinear for gadobenate and gadofosveset secondary to CR interactions with the serum macromolecule albumin, and was well described by an analytical expression for effective 1:1 binding stoichiometry. In whole blood, the 1H2O R1 [CR]‐dependence was markedly non‐linear for all CRs, and was well‐predicted by an expression for equilibrium exchange of water molecules between plasma and intracellular spaces using a priori parameter values only.ConclusionIn whole blood, 1H2O R1 exhibits a nonlinear relationship with [CR] over 0 to 18 mM CR. The nonlinearity is well described by exchange of water between erythrocyte and plasma compartments, and is particularly evident for high relaxivity CRs. Magn Reson Med 72:1746–1754, 2014. © 2013 Wiley Periodicals, Inc.