Serum thyroid hormone and TSH concentrations were measured before and after oral TRH (40 mg) administration in 46 women with preclinical hypothyroidism. Preclinical hypothyroidism was defined as serum T4 in the normal range, a normal or elevated basal serum TSH, and an exaggerated serum TSH response to TRH, in the absence of clinical manifestations of hypothyroidism. The results were compared to those in 22 normal women of the same age and body mass index. Overall, the patients had significantly lower mean values for basal T4 [total T4, free T4 index (FT4 index), and free T4] but not for T3; all indices of T4 were lower in those with an elevated basal TSH, but only the FT4 was lower in patients who had normal basal TSH levels and exaggerated TSH responses to TRH. Thyroid reserve, or the increase in serum thyroid hormones after TRH (delta T4, delta FT4, and delta T3) showed an inverse correlation with basal TSH (for delta T4, r = -0.518 and P less than 0.001; for delta FT4, r = -0.442 and P less than 0.05; for delta T3, r = -0.645 and P less than 0.001). Thyroid reserve was lower than normal in those with elevated basal TSH levels, but was normal in those with exaggerated TSH responses to TRH who had normal basal TSH levels. Thus, an elevated basal TSH level, even with basal serum T4 and T3 levels in the normal range, indicates deficient thyroid reserve.