Recent reports of altered TSH responsiveness to its releasing hormone (TRH) in women with premenstrual syndrome (PMS) suggested that subclinical hypothyroidism may be responsible for the mood changes, such as depression, that occur in these women. In this study we measured basal and TRH-stimulated serum TSH and PRL levels in 15 women with PMS and in 19 age-matched normal women. The mean baseline serum TSH concentrations were similar in the 2 groups in both the follicular [normal, 1.3 +/- 0.2 (+/- SE); PMS, 0.9 +/- 0.2 mU/L] and luteal (normal, 1.1 +/- 0.2; PMS, 1.1 +/- 0.2 mU/L) phases of the cycle. The mean baseline serum PRL levels also were similar in the 2 groups in the follicular (normal, 16 +/- 2; PMS, 13 +/- 2 micrograms/L) and luteal (normal, 13 +/- 2; PMS, 14 +/- 2 micrograms/L) phases of the cycle. After TRH administration, peak serum PRL and TSH levels were reached at 15 and 30 min, respectively, and the response curves were virtually identical in the 2 groups in both phases of the cycle. One normal woman had elevated basal and TRH-stimulated TSH concentrations compatible with subclinical hypothyroidism, but had normal noncyclic scores on her prospective rating scales. Our findings suggest that PMS is not associated with thyroid dysfunction or abnormal PRL secretion and that thyroid hormone replacement therapy is not indicated in this condition.