Fibrosing colonopathy, a recently described complication of patients with cystic fibrosis, manifests clinically approximately 7-12 months after starting high dose pancreatic enzyme treatment. Although the pathogenesis of fibrosing colonopathy is unknown, it is highly correlated with pancreatic enzyme dose. In this study, immune mediated factors which may be associated with fibrosing colonopathy were explored. Sera from 14 patients with cystic fibrosis and meconium ileus were collected at diagnosis and then longitudinally for four to five years after enzyme treatment. Sera were analysed for total IgG and antiporcine trypsin IgG using an ELISA assay. Before enzyme treatment, serum antiporcine trypsin IgG concentrations were negligible, at 2.9 (SD 0.3) micrograms/ml. Thirteen patients (93%) developed a significant antibody response to porcine trypsin after starting enzyme treatment, reaching a peak concentration of 69.4 (20.1) micrograms/ml 7-12 months after the introduction of enzymes. Since peak IgG concentrations coincided with published reports of time of onset of symptoms of fibrosing colonopathy, local injury by protease or by immune mediated mechanisms may be responsible for the pathological changes in this iatrogenic disease.