Severe, acute pancreatitis is commonly associated with a systemic illness which may result in multiple organ failure. There is evidence that an aberrant immune response, involving increased secretion of proinflammatory cytokines from activated monocytes and mononuclear phagocytes, is responsible for another systemic illness--septic shock. Previous studies have investigated whether there is a correlation between plasma cytokine levels and severity of pancreatitis. However, these results may not reflect mononuclear phagocyte activation. In this paper, monocytes (collected from patients with severe pancreatitis) were cultured in vitro and secreted cytokine levels measured after 24 hours by ELISA. Secretion of tumour necrosis factor alpha, interleukin-6 and interleukin-8 was higher in cells taken from patients who later developed systemic complications. There was no difference in the secretion of interleukin-1 beta. The mechanism by which mononuclear phagocytes are activated in acute pancreatitis, and the role of genetic predisposition, are discussed.