Excess perinatal morbidity and mortality continue to be major problems in developed and developing nations. Most perinatal deaths occur in infants born weighing less than 2500 g. Large expenditures of time, equipment, and personnel have led to striking reductions in neonatal mortality. However, rates of prematurity have not declined. Exploration of proven causes of prematurity and low birth weight suggests a role for infection that has hitherto not received sufficient attention. Women with symptomatic pyelonephritis, even when treated promptly, experience an excess of prematurity and perinatal death, and their children have lowered intelligence scores and neurologic scores. Women with asymptomatic bacteriuria experience higher rates of low birth weight and perinatal mortality, as well as symptomatic pyelonephritis, and these are preventable by screening and treatment during pregnancy. Recent evidence also suggests that genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis) are a cause of prematurity and that treatment of women colonized with these organisms results in significant reduction in prematurity rates.