It has been suggested that weight change might be associated with certain neuroendocrine abnormalities often observed in patients suering from a depressive illness. This preliminary study examined whether objective measures of weight change were associated with dexamethasone suppression test (DST) results or plasma levels of thyroid hormones, and whether they correlated with clinical improvement. Speciยฎc measures included plasma cortisol following dexamethasone, plasma free thyroxine (T4) and triiodothyronine (T3), as well as anthropometric measures (skinfolds, percentage body fat, body density). The majority of patients (75 per cent) showed some weight gain after treatment. A strong positive correlation was observed between weight gain and plasma tricyclic levels P 0ร005 but only a weak correlation was found between plasma tricyclic levels and therapeutic response r 0ร14. A gender dierence was seen in the relationship between weight gain and therapeutic response, with weight gain being associated with less improvement in men and more improvement in women. Therefore, weight gain during treatment may not necessarily indicate clinical improvement for all patients. The only variable that reliably predicted treatment response was free T4. High levels of free T4 prior to treatment were highly correlated with better clinical status as indicated by HAMD scores r 0ร87, P 0ร005. Following treatment with imipramine, plasma cortisol levels after dexamethasone administration were reduced in treatment responders but not in nonresponders. Overall, patients that showed the largest decreases in post-dexamethasone cortisol levels from before to after treatment also showed the largest decreases in HAMD total scores r 0ร37 and, especially, somatic anxiety scores r 0ร58, p `0ร05. These eects were stronger in women than men.