Antibodies raised against the cystic fibrosis transmembrane regulator protein (CFTR) were used to localize CFTR in intestinal tissues of piglets and mice. Positive staining for CFTR was detected in goblet cells of both species. A second population of epithelial cells of unknown phenotype was also labeled by anti-CFTR antibodies. The labeling pattern was abolished by preincubation of anti-CFTR antibodies with the immunogen or when non-immune IgG was used in place of anti-CFTR antibodies. These results support other studies that suggest that alterations in goblet cell function may be involved in the intestinal abnormalities associated with cystic fibrosis.