We attempted to identify a structural correlate of the pulmonary hypertension observed in newborn infants of diabetic mothers (IDM) by performing a morphometric analysis of pulmonary arteries at the transition of terminal to respiratory bronchiolus (TRB) in postmortem lungs of 20 IDM and 14 control infants. Although there was no readily apparent microscopic difference between the lungs of newborn IDM and controls, the degree of muscularization, as measured by mean medial area (MMA) of 10 TRB arteries, was significantly greater in preterm IDM (gestational age < or = 37 weeks) than in age-matched controls (502 versus 341 microns 2; P = .0038). Among infants of gestational age > 37 weeks, there was no significant difference between MMA in IDM (508 microns 2) and MMA in controls (598 microns 2). These findings point at an accelerated muscularization of the TRB arteries in IDM, apparent early in the third trimester. The pathogenesis of this hypermuscularization is not understood, but smooth muscle growth promoters such as insulin may play a role. The abnormal timing of TRB artery muscularization could be a manifestation of the basic disturbance in development that contributes to the pulmonary hypertension observed in newborn IDM and to the respiratory difficulties commonly experienced by these infants.