From an endocrine outpatient clinic and psychiatric outpatient clinic in Kaunas, Lithuania, 41 women with major depression were selected for study. Three groups of depressed women were established: 15 with autoimmune thyroiditis (AIT); 13 with diffuse non-toxic goiter (DNG); 13 with no thyroid disease (NTD). Standard biochemical tests were used to exclude patients with overt hypothyroidism or overt hyperthyroidism. At baseline the three groups were similar in age and almost identical in severity of depression. In part because of exclusion criteria, all baseline biochemical measures were similar. However, a slight elevation of thyroid-stimulating hormone (TSH) in the AIT group was noted and considered to indicate a tendency toward subclinical hypothyroidism. After thyrotropin-releasing hormone (TRH) administration, six AIT women and six DNG women, but no NTD women, showed blunted TSH responses. As a group DNG women showed smaller TRH responses than other women. Four AIT women showed exaggerated TSH responses. In all three groups basal TSH correlated positively with TSH response to TRH. Basal prolactin (PRL) responses to TRH infusion were similar in all three groups. However, the four AIT women with enhanced TSH responses also showed enhanced PRL responses. Indeed, in the AIT group, but only in this group, PRL responses were correlated with both TSH and basal TSH. In all groups of women the PRL response was unrelated to basal PRL.