We investigated three possible causes of the increased ratio of amylase/creatinine clearance observed in acute pancreatitis. The presence of rapidly cleared isoamylase was excluded by studies of serum and urine, which demonstrated no anomalous isoamylases. In pancreatitis, the ratios (Â±1 S.E.M.) of both pancreatic isoamylase (9.2Â±0.6 per cent) and salivary isoamylase (8.6Â±1.6 per cent) were significantly (P<0.01) elevated over respective control values (2.4Â±0.2 and 1.8Â±0.2 per cent). Increased glomerular permeability to amylase was excluded by the demonstration of normal renal clearance of dextrans. We tested tubular reabsorption of protein by measuring the renal clearance of Î²2-microglobulin, which is relatively freely filtered at the glomerulus and then avidly reabsorbed by the normal tubule. During acute pancreatitis the ratio of the renal clearance of Î²2-microglobulin to that of creatinine was 1.22Â±0.52 per cent, an 80-fold increase over normal (0.015Â±0.002 per cent), with a rapid return toward normal during convalescence. Presumably, this reversible renal tubular defect also reduces amylase reabsorption and accounts for the elevated renal clearance of amylase/creatinine observed in acute pancreatitis. (N Engl J Med 295:1214-1217, 1976). Patients with acute pancreatitis have an elevated renal clearance of amylase relative to creatinine (CAm/Ccr),1 2and it is this increased clearance that makes the urinary amylase a more sensitive indicator of pancreatitis than the serum level. Recently, Warshaw and Fuller3proposed that measurement of the CAm/Ccrratio is of diagnostic value in patients with hyperamylasemia since only subjects judged to have pancreatitis had an elevated ratio. There appear to be at least three possible mechanisms whereby the CAm/Ccrratio might become elevated in pancreatitis: an increased serum concentration of a.