To define the course of neonatal circulatory transition and to identify clinically relevant echocardiographic measurements in the diagnosis of persistent pulmonary hypertension, we prospectively studied 32 healthy term infants from 30 minutes to 24 hours after birth with color and quantitative Doppler echocardiography on the first day of life, and compared them with 33 term infants supported by mechanical ventilation for respiratory failure. Color Doppler imaging included measurements of cardiac output, left pulmonary artery flow, aortopulmonary pressure difference, ductal flow, left-to-right color-flow jet area of the ductus arteriosus, and ductal flow characteristics. In healthy infants the majority of measurable changes in cardiopulmonary hemodynamics had occurred by 8 hours after birth, although some degree of right-to-left ductal shunting was found up to 12 hours after birth. In the infants with respiratory failure, ductal flow and maximum aortopulmonary pressure difference measurements at 8, 12, and 24 hours showed a significant delay in ductal closure and a high incidence of persistent pulmonary hypertension, which correlated well with the severity of their respiratory failure. Factors such as aortopulmonary pressure difference, prolonged right-to-left shunting with decreased left pulmonary artery flow, and failure to develop a left-to-right ductal color-flow jet were found to be practical markers for assessing the course of neonatal circulatory transition in sick term infants.