Three patients with clinical and radiologic evidence of pancreatic necrosis or peripancreatic fluid collections/inflammatory masses who were advised to have surgery on the basis of bacterial infection on skinny-needle aspiration of the pancreas but were deemed medically unstable or refused operative intervention were treated with intensive antibiotic therapy. All three patients survived the attack of acute pancreatitis with infection on medical therapy alone. This suggests that occasional patients with infected necrosis and/or peripancreatic collections/inflammatory masses may respond to antibiotics, especially those antibiotics that have recently been shown to have a high penetration into pancreatic tissue.