Lutzomyia longipalpis expresses a salivary protein called maxadilan (MAX) that functions to dilate vertebrate blood vessels and thereby to facilitate the sand fly's acquisition of blood. We hypothesized that antibodies specific for one of many MAX variants would inhibit vasodilatory function of that variant. In vitro and in vivo experiments showed that antibodies against a specific MAX variant decreased vasodilatory function. More specifically, antibodies against MAX blocked vasodilation of a constricted rabbit aorta. Additionally, a strain of Lu. longipalpis, with a nearly uniform MAX genotype, obtained a larger blood meal from naive BALB/c mice compared with mice that were either immunized with a homologous MAX genotype or sensitized to bites of flies from the same strain. Those flies taking blood from mice sensitized by sand fly bites also laid significantly fewer eggs than when they took blood from naive mice. These results have potential epidemiologic importance in light of the potential use of MAX in a vaccine or as part of a diagnostic test because they imply that a uniform MAX genotype is selected against by the vertebrate host immune response and that antigenic diversity is selected for.