BACKGROUND: Clostridium perfringens is a bowel commensal that can colonise the biliary tract. It produces the alpha toxin (phospholipase C), which can induce spontaneous tissue necrosis. AIMS: To investigate whether there is any evidence that Clostridium perfringens alpha toxin can be detected in acute pancreatitis. METHODS: Serum samples from 21 patients with acute pancreatitis and 22 controls were assayed for C perfringens phospholipase C as well as anti-phospholipase C IgG and IgM; IgG and IgM anti-toxins were measured by enzyme linked immunosorbent assay. RESULTS: In normal healthy controls there is a very high level of natural anti-toxin of both the IgG and IgM class. Of the 21 patients with acute pancreatitis alpha toxin was detected in five (23.8%). Levels of both IgG and IgM anti-toxin were significantly reduced in acute pancreatitis. CONCLUSIONS: The results suggest that there is an abnormality of the immune status to C perfringens alpha toxin in patients with acute pancreatitis. This may be the result of a release of alpha toxin, although it is difficult to state whether this is a primary or secondary phenomenon in these patients. These preliminary results merit further investigation.