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OBJECTIVE--To examine the concentration of circulating tumour necrosis factor alpha (TNF alpha) in patients with severe congestive heart failure (New York Heart Association class IV) during one year and to correlate changes in this cytokine with changes in plasma noradrenaline, plasma renin activity, and weight. DESIGN--A prospective study of the role of TNF alpha in severe chronic heart failure. Blood samples were collected at intervals of three months. SETTING--Medical research centre of a teaching hospital. PATIENTS--16 patients with chronic stable severe heart failure. INTERVENTIONS--Vasodilator treatment with captopril or flosequinan. MAIN OUTCOME MEASURES--Changes in TNF alpha and the correlation with changes in plasma noradrenaline, plasma renin activity, and weight during optimal medical treatment for one year. RESULTS--The mean concentration of TNF alpha was greater than the upper 95% confidence interval for healthy controls throughout the year of the study but there was considerable between and within patient variation. No correlation was seen between TNF alpha and plasma noradrenaline, plasma renin activity, or weight. CONCLUSIONS--The stimulus resulting in enhanced plasma concentrations of TNF alpha in congestive heart failure remains unclear and concentrations at any particular time were not prognostic.