The results of a Coombs test on each infant, age of onset of jaundice, and of maximum recorded serum indirect bilirubin concentration were statisically analyzed on 2,428 consecutive newborn infants who were Rh compatible with their mothers and who weighed 2.5 kg or more. The incidence of ABO isoimmune hemolytic disease was estimated by subtracting the frequency of each of these observations in ABO compatible infants from the corresponding frequency in ABO incompatible infants. This subtraction decreased the contribution of extraneous causes for jaundice and a positive Coombs reaction. As expected, these signs of hemolytic disease were found more often in ABO incompatible infants than in compatible infants. Whether detected by a positive Coombs reaction, jaundice in the first 24 hours, serum bilirubin concentrations over 10 mg/dl, or any combination thereof, the incidence of ABO disease was much higher in black neonates than in white ones. These findings indicate that early discharge of newborn infants from the hospital should not be authorized without specific assessments, especially when the infant is ABO incompatible and black.