Ureaplasma urealyticum is a common component of the vaginal flora during pregnancy. Transmission of U. urealyticum to the low birth weight infant may contribute to neonatal respiratory disease. We studied prospectively 111 infants with birth weights of 2 kg or less who were consecutively admitted to a neonatal intensive care unit during a 7-month period. The infants had eye, throat, vagina and/or rectum cultured for U. urealyticum on days 1, 3 and 7 and weekly thereafter until the time of discharge. Forty-six infants (41%) had at least one culture site positive for U. urealyticum (eye, 9%; throat, 35%; vagina, 34%; and rectum, 13%). Respiratory distress at birth was not associated with U. urealyticum colonization. However, colonization with U. urealyticum was significantly associated with the development of chronic lung disease. Of the infants colonized with U. urealyticum 30% developed chronic lung disease, whereas 8% of those not colonized developed chronic lung disease (P less than 0.05). Duration of positive pressure ventilation and oxygen therapy could not account for the higher incidence of chronic lung disease in the infants colonized with U. urealyticum. Stepwise logistic regression analysis using the profiles of birth weight, need for intubation and status of colonization with U. urealyticum correctly identified 79% of the infants who developed chronic lung disease. Additional studies serologic techniques are needed to confirm the association of U. urealyticum colonization and chronic lung disease in low birth weight infants.