To investigate the etiologic role of iodine intake in postpartum thyroiditis (PPT), we have measured postpartum urinary iodine excretion serially in a large prospective study of PPT. A total of 1996 women were screened for thyroid microsomal antibody during the second trimester of pregnancy. One hundred fifty-two of the 235 antibody-positive women and an equal number of age-matched antibody-negative controls were followed postpartum with measurements of urinary iodine and thyroid function at monthly intervals for 12 months. Iodine excretion in the immediate postpartum period did not differ between the 73 women who developed PPT and the antibody-negative controls. In women with PPT with hyperthyroidism, hypothyroidism, or hyperthyroidism followed by hypothyroidism, increased urinary iodine excretion was observed between 8 and 16 weeks postpartum, which preceded the hormonal disturbances among the women with hypothyroidism. The height of the rise in urinary iodine excretion during the first 20 weeks postpartum correlated with the serum free thyroxine levels (r = 0.61, p less than 0.001). Iodine intake is unlikely to affect the prevalence of PPT. However, these data show that the hyperthyroid phase of PPT is associated with a significant release of intrathyroidal iodine due to thyroid destruction and that the same process also occurs to a lesser extent before the hormonal disturbances associated with hypothyroid PPT.