Ureaplasma urealyticum was isolated from the lower respiratory tract of three infants with persistent pulmonary hypertension of the newborn. In one, cultures positive for U urealyticum were obtained on multiple occasions from trachea, blood, and pleural fluid prior to the infant's death on postnatal day 6. Autopsy findings confirmed the presence of severe pneumonia and the organism was again recovered from multiple sites. A second infant had no apparent predisposing factors for development of persistent pulmonary hypertension of the newborn but U urealyticum and Staphylococcus epidermidis were recovered from the trachea antemortem and from lung tissue obtained during autopsy on the 12th postnatal day. The third infant had persistent pulmonary hypertension of the newborn and a pulmonary infiltrate within hours after birth with tracheal cultures positive for both U urealyticum and Mycoplasma hominis. Erythromycin was given for ten days, and the infant gradually improved. Prolonged ventilation with supplemental oxygen was necessary, and chronic lung disease developed. This is the first report of neonatal ureaplasmal pneumonia with sepsis and persistent pulmonary hypertension of the newborn as well as the first time a microorganism other than streptococci has been specifically implicated in the pathogenesis of persistent pulmonary hypertension of the newborn. Respiratory infections with U urealyticum or other bacteria should be considered as possible causative or contributory factors in infants with persistent pulmonary hypertension of the newborn.