Epidemiology data have revealed a higher prevalence of nodular goiters in women than men in both iodine-sufficient and iodine-deficient areas. Increased prevalence of thyroid nodules has also been reported in women with higher gravidity. However, the association between pregnancy and thyroid nodule formation has never been studied. The aim of our study was to evaluate the incidence of thyroid nodules during pregnancy and determine whether pregnancy will induce thyroid nodule formation. Two hundred twenty-one healthy southern Chinese women in the first trimester of their pregnancy were studied prospectively. Thyroid ultrasonography, thyroid function tests, and urinary iodine excretion were measured at first, second, and third trimesters of pregnancy as well as 6 wk and 3 months postpartum. Thyroid nodules (>2 mm in any dimension on ultrasonography) were detected in 34 (15.3%) subjects at first trimester, with 12 (5.4%) subjects having more than one nodule. Eight subjects had clinically palpable nodules. Women with thyroid nodules were older (P < 0.01) and had higher gravidity (P < 0.02) than those women without thyroid nodules. The volume of the single/dominant nodules increased from 60 (14--344) mm(3), median (interquartile range) at first trimester to 65 (26-472) mm(3) at third trimester (P < 0.02). These nodules remained enlarged at 103 (25-461) mm(3) 6 wk postpartum (P < 0.005) and 73 (22-344) mm(3) at 3 months postpartum (P < 0.05). Patients with thyroid nodules had lower serum TSH values (P < 0.03) and higher Tg levels (P < 0.05) throughout pregnancy. Appearance of new nodules was detected in 25 (11.3%) women as pregnancy advanced so that by 3 months postpartum, the incidence of thyroid nodular disease was 24.4% (P < 0.02 vs. first trimester). Compared with those with no detectable nodules throughout pregnancy, subjects with new nodule formation had higher urinary iodine excretion from second trimester onward (P all < 0.05). However, no difference could be detected in their TSH and Tg levels throughout pregnancy. Fine-needle aspiration on nodules greater than 5 mm in any dimension after delivery (n = 21) confirmed the majority having histological features consistent with nodular hyperplasia. No thyroid malignancy was detected. In conclusion, pregnancy is associated with an increase in the size of preexisting thyroid nodules as well as new thyroid nodule formation. This may predispose to multinodular goiter in later life.