An intervention for infant irritability or colic was evaluated in a randomized clinical trial. A total of 121 full-term irritable infants (2 to 6 weeks old) were randomized to routine care or the home-based intervention program. A third group (n=43) of irritable infants were entered into a post-test-only group. Following the 4-week intervention, the treatment group infants cried 1.7 hours less per day than the infants in the control group (p=0.02). The findings support the emerging view of infant colic as a behavioral pattern that is responsive to environmental modification and structured cue-based care.