SUMMARY The syndrome of delayed anaphylaxis to red meat, i.e. the alpha-gal syndrome (AGS), is found exclusively in patients who have serum IgE antibody (ab) to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). This form of sensitization is related to bites of the tick Amblyomma americanum, however other ticks appear to be relevant in other countries. The objective of the parent study is to investigate the epidemiology, etiology, immunology and clinical features of AGS which is now known to be common in a large area of the USA. In this supplemental application we propose to build off existing cross-sectional cohort studies to carry out prospective longitudinal studies on AGS patients. We will also prospectively follow individuals from the community at-risk for alpha-gal sensitization on the basis of tick bite history. This research will provide important information about clinical and immunologic aspects of AGS natural history. In addition, we propose to collaborate with colleagues in Vascular and Cardiovascular surgery to investigate alpha-gal antibody responses in patients undergoing implantation of biologic grafts or valves. The goal is to determine whether implantation of porcine or bovine-derived biologics (which contain alpha-gal) can induce IgE and/or IgG antibodies to alpha-gal. We will also follow these patients over time to determine if graft or valve failure is more common in patients with high-level antibody responses to alpha-gal.