Serum concentrations of free fatty acids (FFA) were assayed in 20 patients with acute necrotizing pancreatitis (ANP). Pancreatic and peripancreatic fat necrosis was verified on operation and/or by contrast-enhanced computed tomography. For comparison, 20 patients with acute edematous pancreatitis (AEP) were examined. On admission, FFA serum levels were 1.14 +/- 0.12 (SEM) mmol/L in ANP and, thus, significantly (p < 0.03) higher than in AEP (0.78 +/- 0.09 mmol/L). The two groups also differed in the later course: in ANP, the FFA values remained raised (d 5-11:0.86 +/- 0.13 mmol/L; p > 0.05 vs day 1), whereas in AEP, the FFA concentrations normalized within 1 wk (d 2-4:0.52 +/- 0.11 mmol/L; d 5-11:0.39 +/- 0.05 mmol/L; p < 0.05 vs day 1 and p < 0.01 vs ANP). Serum FFA correlated positively with C-reactive protein levels (rs = 0.42; p < 0.01), but has less discriminating potency between ANP and AEP. In AEP, the initial peak may correspond to the disease outburst itself and to unspecific stress. In ANP, the higher and sustained elevation of FFA may predominantly mirror the ongoing pancreatic parenchymal and extrapancreatic fat necrosis, and be pathophysiologically relevant, especially in view of significantly reduced serum albumin levels in ANP.