Because infants with colic appear to have abdominal pain similar to that of adults with irritable bowel syndrome, who may benefit from the addition of fiber to their diet, we tested whether fiber added to infant formula would alleviate colic. Twenty-seven normal, term infants (aged 2 to 8 weeks; 14 girls) with colic, defined as crying plus fussing for more than 3 hours a day for at least 3 days of a 6-day baseline period, were enrolled. Infants were randomly assigned in 9-day periods to a sequence of placebo (Isomil formula) followed by fiber-supplemented formula (Isomil plus soy polysaccharide) (n = 12) or the reverse (n = 15). Daily diaries of crying, fussing, sleeping, formula, intake, and stooling were kept. Twenty-two infants completed three lactulose breath hydrogen tests at the end of the baseline period and after each study period. The crossover trial was followed by 30 to 35 days of use of the study formula chosen by the parents as most beneficial but unknown to the investigators. Growth was monitored throughout. Serum cholesterol, calcium, phosphate, albumin, iron, and zinc concentrations were measured at the conclusion. There were no significant differences in average daily time spent by the infants in fussing and crying during ingestion of the fiber-supplemented formula. However, parents of 18 of 27 infants chose fiber-supplemented formula as most beneficial in ameliorating symptoms of colic. While the infants were consuming fiber-supplemented formula, stool frequency increased, and breath hydrogen excretion increased significantly, in response to lactulose. Growth and serum biochemical measurements were normal in all infants. Supplementation of infant formula with the level of soy polysaccharide used in this study may have reduced crying and fussing in some infants but did not affect colicky behavior in the majority of infants, who continued to cry and fuss excessively.