We studied the usefulness of anorectal manometry in excluding Hirschsprung's disease in 25 neonates with signs and symptoms of intestinal obstruction. An intraluminal pressure transducer or perfused side-opening catheters were used to evaluate anal tone, anal rhythmicity, and internal sphincter relaxation during rectal distention. Hirschsprung's disease was diagnosed by rectal biopsy in 16% of the neonates. Studies using anorectal manometry gave one false positive and one false negative diagnosis of Hirschsprung's disease, which resulted in 75% sensitivity, 95% specificity, and a kappa coefficient of 0.7. We found that anorectal manometry, a rapid and atraumatic test, is a reliable screening test for exclusion of neonatal Hirschsprung's disease. By using the combination of manometry and contrast enema, it is possible to eliminate the need for a confirmatory rectal biopsy in many neonates suspected of having Hirschsprung's disease.