We demonstrate that tumor tissues derived from patients with pancreatic cancer over-express receptors for interleukin-4 in situ at high density, as assessed by immunohistochemical staining using an anti IL-4 receptor antibody. On the other hand, four of five normal pancreas specimens did not stain with anti IL-4 receptor antibody, while one specimen showed weak to moderate staining. Using the approach of selective receptor targeting, we have tested the efficacy of a recombinant cytotoxin IL4-PE, which is composed of a targeting moiety (interleukin-4) and a mutated form of Pseudomonas exotoxin. Our results demonstrate that this molecule exerts vigorous antitumor activity against human pancreatic tumors implanted subcutaneously or orthotopically in immunodeficient animals. Thus, IL-4 receptor-targeted cytotoxin may provide an effective therapy for the treatment of pancreatic cancer. For details, see the article by Kawakami et al. on page 3575 of this issue.