In this open, controlled, prospective study, 28 infants with colic were randomized to either cranial osteopathic manipulation or no treatment; all were seen once weekly for 4 weeks. Treatment was according to individual findings, and administered by the same practitioner. Parents recorded time spent crying, sleeping and being held/rocked on a 24-hour diary. A progressive, highly significant reduction between weeks 1 and 4 in crying (hours/24h) was detected (P<0.001) in treated infants; similarly, there was a significant improvement in time spent sleeping (P<0.002). By contrast, no significant differences were detected in these variables for the control group. Overall decline in crying was 63% and 23%, respectively, for treated and controls; improvement in sleeping was 11% and 2%. Treated infants also required less parental attention than the untreated group. In conclusion, this preliminary study suggests that cranial osteopathic treatment can benefit infants with colic; a larger, double-blind study is warranted.