The present study evaluated serum ribonuclease activity (SRA) in patients with inflammatory and neoplastic pancreatic diseases. RNase determination was carried out using t-RNA (T) from E. coli MRE 600 at pH 7.4 and polycytidylic acid (poly-C) (P) at pH 6.6 as RNA substrates with RNase A from bovine pancreas as reference enzyme. Healthy volunteers had a SRA of T: 160 +/- 12 and P: 482 +/- 24 ngeq/mL (mean +/- SEM (n]. In patients with acute interstitial pancreatitis (AIP), SRA was similar to healthy controls (T: 166 +/- 14; P: 474 +/- 30 ngeq/mL). Patients with acute necrotizing pancreatitis (ANP) had increased SRA (T: 278 +/- 49; P: 791 +/- 145 ngeq/mL, p less than 0.01, compared to controls). SRA values were also increased in patients with chronic pancreatitis (CP) with T: 224 +/- 15 ngeq/mL (p less than 0.01) and in patients with pancreatic carcinoma (PCA) with T: 331 +/- 35 (p less than 0.001 vs controls, p less than 0.01 vs CP). Increased SRA was detected in patients with renal insufficiency (T: 2576 +/- 195 ngeq/mL, p less than 0.001). Diagnostic discrimination between AIP and ANP was achieved in 69% using T-SRA (sensitivity 31%, specificity 88%), and in 78% using P-SRA (sensitivity 54%, specificity 92%). Discrimination between CP and pancreatic carcinoma was possible in 68% (sensitivity 67%, specificity 71%). The diagnostic value of serum RNase is limited because of its low sensitivity, but increased T-SRA above a cutoff of 250 ngeq/mL and increased P-SRA above a cutoff of 620 ngeq/mL are specific for detecting pancreatic necrosis in the absence of renal impairment. The kidney is a major site for SRA clearance.