In the present study, we assessed the use of urinary natriuretic peptides [N-terminal proatrial natriuretic peptide (N-ANP) and N-terminal pro-brain natriuretic peptide (N-BNP) and C-type natriuretic peptide (CNP)] in the diagnosis of heart failure. Thirty-four consecutive hospitalized heart failure patients (median age, 75.5 years; 14 female) were compared with 82 age- and gender-matched echocardiographically normal controls. All subjects provided plasma and urine specimens. Plasma was assayed for N-BNP, and urine was assayed for N-ANP, N-BNP and CNP. The diagnostic efficiency of peptides was assessed using receiver operating characteristic (ROC) curve analysis. All three urinary natriuretic peptides were significantly elevated in heart failure patients ( P <0.001). Urine N-BNP was correlated with plasma N-BNP ( r (s)=0.53, P <0.0005). Areas under the ROC curves for urinary N-ANP, N-BNP and CNP were 0.86, 0.93 and 0.70 and for plasma N-BNP was 0.96. Correcting urinary peptide levels using urine creatinine produced ROC areas of 0.89, 0.93 and 0.76 respectively. A urine N-BNP level cut-off point of 11.6 fmol/ml had a sensitivity and specificity for heart failure detection of 97% and 78% respectively, with positive and negative predictive values of 64.7 and 98%. In conclusion, although all three natriuretic peptides were elevated in urine in heart failure, urinary N-BNP had diagnostic accuracy comparable with plasma N-BNP. Use of urinary N-BNP for heart failure diagnosis may be suitable for high-throughput screening, especially in subjects reluctant to provide blood samples.