Background: The effect of diet change in 38 bottle-fed and 77 breast-fed “colicky” infants, referred from community-based pediatric facilities was studied over a 1-week period in a double-blind (within each feeding mode), randomized, placebo-controlled trial. Methods: Bottle-fed infants were assigned to either casein hydrolysate or cow's milk formula. All mothers of breast-fed infants were started on an artificial color-free, preservative-free, additive-free diet and also randomized to an active low allergen diet (milk-, egg-, wheat-, nut-free) or a control diet. Results: The response to diet was assessed on day 1 and day 8 with the use of a previously validated infant distress chart on which parents recorded distress levels. If successful outcome was defined as a reduction in distress of 25% or more, after adjusting for age and feeding mode, infants on active diet had a significantly higher rate of improvement than those on the control diet (odds ratio, 2.32; 95% confidence interval, 1.07-5.0; p = 0.03). Analysis of the day 8 to day 1 distress ratio, again adjusted for age and feeding mode, showed that infants on the active diet had distress reduced by 39% (95% confidence interval, 26-50) compared with 16% (95% confidence interval, 0-30) for those on the control diet (p = 0.012). Conclusion: The results suggest a period of dietary modification with a low allergen diet and appropriate nutritional support should be considered in healthy infants with colic. (J ALLERGY CLIN IMMUNOL 1995;96:886-92.)