As part of a large, multicenter study of newborn cry analysis and Sudden Infant Death Syndrome, we examined the effects of in utero cocaine exposure on ten acoustical cry characteristics. Newborn cry recording and medical record review was performed for 23,948 newborns. Cocaine use during pregnancy (determined by record review) was identified in 438 (1.8%) women (310 by self-report only; 128 newborns also had positive urine assay). A demographically similar group of 373 newborns, selected from the 23,510 newborns without known cocaine exposure, made up the comparison group. Cry analysis was technically possible for 768 recordings: 404 cocaine-exposed and 364 non-exposed controls. Comparison of cocaine-exposed vs control newborns, after adjustment for potential confounding variables, found significant differences including: fewer cry utterances (P = .001), more short cries (P = .02), and less crying in the hyperphonation mode (P = .01), for the cocaine-exposed neonates. As reported in other studies, cocaine-exposed newborns also were significantly lower in birth weight, length, and head circumference. Newborns who had positive urine tests for cocaine suffered the greatest effects on both cry and growth parameters. These findings suggest a pattern of underaroused neurobehavioral function and are consistent with the emerging picture of the adverse neurobehavioral effects of cocaine. Developmental outcome studies are in progress to determine if acoustical analysis of the newborn cry can be used to identify cocaine-exposed newborns who are at highest risk for poor outcome.