Over two decades after the discovery. isolation and chemical characterization of the vasoactive intestinal peptide (VIP), much has been learned about its biological properties, its relationship to other neurotransmitters, its mode of action, and its importance in physiological regulation and disease. Not all questions have been answered, however. Our knowledge of the VIP receptors and the second-messenger pathways, e.g. remains incomplete, and the place of VIP in human physiology and disease needs further definition. The work summarized by Paul and Ebadi (1993) addresses two specific facets of the biology of VIP: its binding to calmodulin or calmodulin-like molecules, and its catalysis by anti-VIP antibodies. This critique is meant to complement the accompanying review, amplifying some of the comments, and present them in a broader perspective.