We have performed CT-guided percutaneous needle aspiration in 104 patients with severe pancreatitis strongly suspected of harboring pancreatic infection on the basis of systemic toxicity and CT findings (Balthazar CT grade D or E). Of these 104 patients, 51 (49%) were documented with pancreatic infection. Gram stain was positive in 54 of 58 infected aspirates, and culture was positive in all 58. Klebsiella, Escherichia coli, and Staphylococcus aureus were the most frequent organisms. Eighty-six percent of infected processes contained only one organism. Overall, pancreatic infection was documented by GPA within the first 2 wk in approx one-half of patients. There were no complications. The overall rate of infection decreased from 60 (1980-1987) to 34% (1988-1995) (p = 0.011). This change was caused by a reduction in the rate of infected necrosis from 67 to 32% (p = 0.015). The overall mortality rate remained at 20%. The mortality of sterile pancreatitis was not different from infected pancreatitis (p = 0.14). We conclude that GPA is a safe, accurate method of diagnosis of pancreatic infection. The rate of pancreatic infection appears to be decreasing. The overall mortality of severe pancreatitis among patients suspected of harboring pancreatic infection has remained unchanged because of the high mortality associated with both infected necrosis and severe sterile necrosis.