To determine the relationship between infantile colic and cow's milk protein intolerance (CMPI) in formula-fed infants, 70 infants (38 male, 32 female) were selected, with mean age 30.2 +/- 21.4 days, with severe colic (duration of crying greater than 4 h per day for 5 days per week). In 50 of the infants in the study group (71.4%) there was a remission of symptoms when cow's milk protein (CMP) was eliminated from the diet. Two successive challenges caused the return of symptoms in all these 50 infants. There was a positive anamnesis for atopy in 9 of 50 of the patients with CMP-related colic and in 1 of 20 of those with non-CMP-related colic (p greater than 0.05). A follow-up period of 18 months' mean duration showed that 22 of 50 (44%) of the infants with CMP-related colic and 1 of 20 (5%) of those with non-CMP-related colic developed an overt alimentary intolerance (p less than 0.02). We conclude that a considerable percentage of the infants with severe colic also have CMPI and that in these cases, dietetic treatment should be the first therapeutic approach.