Lithium is widely used and the treatment of choice for patients with manic-depressive illness. For pregnant patients with manic-depressive illness, however, the use of lithium during the first trimester of pregnancy may present an increased risk for fetal maldevelopment. We have recently cared for several large-for-gestational-age, prematurely born infants whose mothers were treated with lithium throughout pregnancy. To determine whether maternal lithium use during pregnancy may predispose to the onset of premature labor and fetal macrosomia, we reviewed records from the International Register of Lithium Babies and from a cohort of manic-depressive pregnant women. More than one third (36%) of infants reported to the International Register were born prematurely, and 37% of the premature infants were large for gestational age; 15% of the term infants were born large for gestational age. In the cohort group, manic-depressive mothers who received lithium during pregnancy had a 2.5-fold higher incidence of premature births than manic-depressive pregnant patients who did not receive lithium treatment. The incidence of large-for-gestational-age births in lithium-treated women in the cohort was not different from that of the general population or from manic-depressive women not treated with lithium. In summary, an association between maternal lithium therapy and premature delivery is reported. We recommend that women receiving lithium therapy during pregnancy be closely monitored for the onset of premature labor.