Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVII.© 2002 Cold Spring Harbor Laboratory Press 0-87969-678-8/02. 223 for differentially expressed cell surface proteins. We isolated from the prostate a potential mimetope of interleukin 11 (IL-11). To test the tissue specificity of the IL-11 peptide mimic, we developed a phage overlay assay to evaluate receptor–ligand interactions in tissue sections. We chose the motif RRAGGS for our studies (Arap et al. 2002). We showed by phage overlay on human tissue sections that the prostate-homing phage displaying an IL-11 peptide mimic specifically bound to the endothelium and to the epithelium of normal prostate, but not to control organs, such as skin. In contrast, a phage selected from the skin (displaying the motif HGGVG) did not bind to prostate tissue; however, this phage specifically recognized blood vessels in the skin. Moreover, the immunostaining pattern obtained with an antibody against human IL-11Rα on normal prostate tissue is undistinguishable from that of the CGRRAGGSC-displaying phage overlay; a control antibody showed no staining in prostate tissue. These findings were recapitulated in multiple tissue sections obtained from several different patients. Finally, using a ligand–receptor-binding assay in vitro, we demonstrate the interaction of the CGRRAGGSC-displaying phage with immobilized IL-11Rα at the protein–protein level. Such binding is specific, since it was inhibited by the native IL-11 ligand in a concentrationdependent manner (Arap et al. 2002). The potential of phage display to identify targeting sequences and receptors has hardly been fully explored. We are now expanding our studies and hope to validate multiple receptor–ligand pairs based on this strategy.