ObjectiveTo more clearly define the relationships between plasma proinflammatory cytokine concentrations, physiologic disturbance, and survival in severely ill patients.DesignProspective, longitudinal, cohort analytic study.SettingTeaching hospital intensive care unit (ICU).PatientsTwo hundred fifty-one consecutive nonselected patients admitted to the ICU.InterventionsNone.Measurements and Main Resultsor=to10 days, and of these 19 patients, 16 patients had prolonged increases of plasma cytokines. Two patients with persistently increased plasma TNF concentrations died. Otherwise, persistently increased plasma cytokine concentrations had a variable relation to daily APACHE scores and to mortality.ConclusionsPlasma cytokine concentrations fluctuate in serious illness and have a poor correlation with derangement of whole body physiology in seriously ill patients. Only the presence of bioactive TNF in plasma was an independent predictor of mortality. Daily measurement of plasma proinflammatory cytokine concentrations is unlikely to have clinical application in the ICU setting, except possibly in specific subgroups of patients.(Crit Care Med 1996; 24:1775-1781)