Pituitary adenylate cyclase activating polypeptide (PACAP) is a peptide hormone that exists in two biologically active forms: PACAP-38 and PACAP-27. Several types of PACAP receptors have been characterized, and these have been classified into three families: the VPAC1, the VPAC2, and the PAC1 receptors. In this study, we used in vivo behavioral assays along with pharmacological inhibitors to investigate the behavior of the lysozyme/PACAP receptor in Tetrahymena. This receptor behaves like a PAC1 receptor in some respects; however, PACAP 6-38 serves as an agonist, rather than an antagonist, for this receptor. These results are consistent with the existence of a generalized polycation receptor rather than a PACAP-specific receptor.