We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydial infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term.