Infant colic is a pediatric disorder of unknown etiology. Colic is characterized by excessive crying and it affects 20% of U.S. infants, whether breast-fed or formula-fed. Colic is important because of infant pain, parental frustration with inconsolable crying, some infant abuse mortality, pediatrician effort, expense, and lack of effective treatment. Since levels of bovine IgG (BGG) in infant formulas and human milk are comparable, and breast milk BGG levels seems to correlated with colic, an investigation of whether dietary BGG might be a major cause of colic is proposed. BGG is the major foreign immunoglobulin in the human diet (often 500 mg/day) and has unique properties of intentional transport, stability, binding to Fc receptors, and immunomodulation. In vitro studies suggest that BGG may profoundly influence the developing mucosal immune system and might initiate colic and certain inflammatory diseases. As one immediate goal, this hypothesis will be tested directly by conducting double-blind placebo-controlled trials comparing infant responses after ingestion of BGG and placebo. Both breast-fed infants and formula-fed infants will be tested and colic responses will be assessed by simplified cry diaries. The effect of maternal consumption of diary products on breast milk levels of BGG and on colic in breast-fed infants will also be studied. Since preliminary data show elevated levels of serum BGG in patients with various forms of colitis, a second goal is to determine whether BGG plays an important role in milk-induced colitis, ulcerative colitis, and eosinophilic gastroenteritis. This will be carried out by analyzing sera of patients during exacerbations of these disorders for levels of BGG will be assessed by RAST assay. Another goal is to better understand how BGG is selectively transported and how BGG may cause colic or other diseases in susceptible individuals. Whether intestinal FcR account for selective BGG absorption will be studied in an animal model using a FcR-deficient mouse strain. How and when selective BGG transport occurs i humans will be investigated by measuring milk and serum levels of BGG at various stages of pregnancy and lactation. A knowledge of the role of ingested bovine IgG in colic and other disorders may lead to better methods of prevention and treatment. This research might also provide insights into etiology of autoimmune diseases (rheumatoid arthritis, Type I diabetes).