When plasma osmolality exceeds 350 milliosmoles per kilogram of plasma water during cardiopulmonary resuscitation, a disproportionate increase in mortality is observed. The increase of plasma osmolality is in part related to the administration of sodium bicarbonate. If iatrogenic risks of alkali therapy are to be minimized, repetitive measurements of plasma osmolality are advised. Therefore, the authors investigated a rapid method for determining osmolality, in which whole blood rather than plasma was utilized, thereby obviating the time required for erythrocyte separation. This study demonstrated that the difference between osmolality measured on whole blood and that measured on plasma were comparable to duplicate measurements of osmolality on plasma. The authors conclude that osmolality measured on whole blood serves as a reliable and accurate estimate of plasma osmolality.