Necrotizing enterocolitis (NEC) is a serious and frequently lethal disease of newborn infants. The conditions necessary for the development of NEC appear to be gastrointestinal mucosal injury, the presence of intraluminal bacteria capable of producing NEC, and oral feedings. Almost all infants who develop NEC have been fed. The incidence of NEC is higher in premature than mature infants and it has been postulated that breast feeding will prevent necrotizing enterocolitis in the human premature infant. The carrageenans are a heterogenous group of sulfated polysaccharides extracted from certain marine plants. "Food grade" carrageenan is used extensively in foods, including infant formulas, yet various carrageenans can: a) produce acute inflammation, b) depress macrophage function and primary immune function, c) inhibit complement, and d) produce cecal and colonic ulceration in experimental animals. Apparently, absorption into tissues is necessary for tissue injury to occur. Gastrointestinal absorption does not occur in adult humans who are resistant to the gastrointestinal inflammatory effects of non-degraded "food grade" carrageenan; however, newborns can absorb large molecular weight substances shortly after birth. Because of this and since we have produced histologic intestinal damage in newborn guinea pigs fed one tenth the dose of carrageenan necessary to produce damage in adult guinea pig, we hypothesize that carrageenan in infant formulas may be a contributing factor in the development of NEC. We propose to: a) study the developmental toxicology of carrageenans in guinea pigs and rats, b) investigate the role of carrageenan absorption and complement activation in this toxicity, and finally c) look for evidence of carrageenan absorption and complement activation in the intestines of infants with NEC.