Critically ill patients often have altered serum levels of thyroid hormones. The present study was undertaken to further define hormonal changes in such patients. Since postmenopausal women have normally elevated gonadotropin levels, this group was chosen as the study population. Thirteen critically ill patients with serum T4 concentrations below 5 micrograms/dl (group I), 16 critically ill patients with T4 concentrations of 5 micrograms/dl or greater (group II), and 19 normal subjects (group III) were studied. Basal gonadotropin levels (FSH and LH) were significantly lower (P less than 0.01) in both critically ill groups. The LH level in group I was 36.5 +/- 39.3 (+/- SD) mIU/ml, in group II it was 45.3 +/- 30.4, and in group III it was 75.3 +/- 24.4. The FSH level in group I was 43.0 +/- 39.7 (+/- SD) mIU/ml, in group II it was 78.0 +/- 37.9, and in group III it was 133.0 +/- 38.2. Most group I patients had LH and FSH concentrations far below the normal postmenopausal range. The response to dynamic testing with TRH and LRH revealed a significantly lower incremental TSH response to TRH in group I (8.0 +/- 5.6 mIU/ml) compared to that in group III (13.7 +/- 2.8; P less than 0.05). However, the maximal responses of FSH and LH to LRH were not different between groups I and III, despite the fact that 2 of 10 group I patients had no response. These data indicate that a subset of patients with the low T4 syndrome have hypogonadotropism, inappropriate to their menopausal state. This suggests that acute critical illness may cause hypothalamic or pituitary dysfunction, only part of which is recognized as the low T4 syndrome. The mechanism for this dysfunction and its importance in contributing to the overall mortality in this group is unknown.