Background:Allergy is a common cause of illness. The effect of feeding different infant formulas on the incidence of atopic disease and food allergy was assessed in a prospective randomized double-blind study of high-risk infants with a family history of atopy.Methods:216 high-risk infants whose mothers had elected not to breast-feed were randomized to receive exclusively a partial whey hydrolysate formula or a conventional cow's milk formula or a soy formula until 6 months of age. Seventy-two high risk infants breast-fed for ≥ 4 months were also studied.Results:Follow-up until 5 years of age showed a significant lowering in the cumulative incidence of atopic disease in the breast-fed (odds ratio 0.422 [0.200-0.891]) and the whey hydrolysate (odds ratio 0.322 [0.159-0.653) groups, compared with the conventional cow's milk group. Soy formula was not effective (odds ratio 0.759 [0.384-1.501]). The occurrence of both eczema and asthma was lowest in the breast-fed and whey hydrolysate groups and was comparable in the cow's milk and soy groups. Similar significant differences were noted in the 18-60 month period prevalence of eczema and asthma. Eczema was less severe in the whey hydrolysate group compared with the other groups. Double-blind placebo-controlled food challenges showed a lower prevalence of food allergy in the whey hydrolysate group compared with the other formula groups.Conclusions:Exclusive breast-feeding or feeding with a partial whey hydrolysate formula is associated with lower incidence of atopic disease and food allergy. This is a cost-effective approach to the prevention of allergic disease in children.