BACKGROUND: Women who are positive for thyroid antibodies in early gestation are prone to post-partum depression, apparently independent of thyroid dysfunction, as measured by serum levels of free thyroxine, free triodothyroxine and thyroid-stimulating hormone. This finding may be due to infrequent monitoring of thyroid function, because hyperthyroidism, hypothyroidism and combinations of both may occur post-partum. AIMS: To test the hypothesis that stabilising thyroid function post-partum by administering daily thyroxine reduces the rate of occurrence and severity of associated depression. METHOD: In a randomised double-blind placebo-controlled trial, 100 microg of thyroxine or placebo was given daily to 446 thyroid-antibody-positive women (342 of whom were compliant) from 6 weeks to 6 months post-partum, assessing their psychiatric and thyroid status at 4-weekly intervals. RESULTS: There was no evidence that thyroxine had any effect on the occurrence of depression. The 6-month period prevalence of depression was similar to that reported previously. CONCLUSIONS: The excess of depression in thyroid-antibody-positive women in the post-partum period is not corrected by daily administration of thyroxine.