During the past 5 years, we have used percutaneous aspiration of peripancreatic fluid collections guided by computed tomography (CT) or ultrasonography (US) to facilitate diagnosis of infection in selected cases. Fifteen of 18 patients undergoing guided needle aspiration had persistent fevers (greater than 38.3 degrees C). The three afebrile patients all had abdominal pain and leukocytosis, and two of the three also had elevated serum amylase levels. Percutaneous aspiration was guided by CT in 14 patients and by US in four. On the basis of aspirate Gram stains and cultures, as well as surgical (15) and percutaneous drainage (1) findings, the final diagnosis was pancreatic abscess in nine patients, infected pseudocyst in four, uninfected pseudocyst in four, and cystadenoma in one. Diagnosis based on percutaneous aspiration was correct in 17 of 18 patients (94%), and no complications could be directly attributed to the procedure. We conclude that CT- or US-guided percutaneous aspiration is a safe and accurate diagnostic procedure for patients with peripancreatic fluid collections in whom secondary infection is suspected.