A synthetic polypeptide (l-Pro-Gly-l-Pro)n with an ordered sequence, previously shown to have physical properties similar to those of collagen2,7, was found to be immunogenic in guinea pig and rabbits. Guinea pigs, immunized with (l-Pro-Gly-l-Pro)n, produced antibodies which cross-reacted by passive cutaneous anaphylaxis with a random copolymer of similar composition (l-Pro66Gly34)n. However, no delayed-type skin cross-reactions between the two synthetic antigens were observed. Antibodies produced early in the course of immunization likewise failed to give cross-reactions. These results are interpreted as showing that the antigen must complement the reactive moiety mediating delayed reactions or the early antibody to a higher degree than the late antibody. In a passive cutaneous anaphylaxis test cross-reactions were also observed between (l-Pro-Gly-l-Pro)n and fish, rat and guinea pig collagens. No cross-reactions between (l-Pro66Gly34)n and collagens or between gelatin and the synthetic polypeptides were observed. The results suggest that the polymer of ordered sequence cross-reacts immunologically with collagen by virtue of the triple helix conformation common to both substances. © 1969.