The acute effect of superior cervical ganglionectomy (SCGx) on the pituitary-thyroid axis was examined in rats subjected to surgery 3–24 h earlier. SCGx caused an abrupt decline in thyroid norepinephrine content (an index of degeneration of sympathetic nerve terminals) to 5–10% of controls between 8 and 16 h. Rats subjected to SCGx 14 h earlier exhibited a significant depression of thyroid 131I uptake, total and free serum T4 levels and serum TSH levels. The injection of 250 mU of bovine TSH, while resulting in similar increases of radioimmunoassayable serum TSH in both SCGx and sham-operated rats, brought about a significant increase of total and free serum T4 only in sham-operated controls; TSH treatment augmented serum T3 levels in both groups. In order to assess the involvement of the pineal gland in the changes of activity of the pituitary-thyroid axis after SCGx, rats were pinealectomized (Px) or sham-Px and 3 days later they were subjected to SCGx or sham-SCGx; all animals were killed at the time of expected degeneration of nerve terminals (i.e. 14 h after SCGx). The depressive effects of SCGx on 131I uptake and free serum T4 levels were observed regardless of whether the pineal was present; in contrast, Px impaired significantly or blocked the effect of SCGx on TSH and total serum T4 levels. Pineal removal resulted in a significant increase of serum T3 levels of SCGx rats. Blood flow estimated from the uptake of a tracer dose of 86Rb diminished significantly in the thyroid and pineal glands of SCGx rats while remaining unchanged in the adenohypophysis or medial basal hypothalamus. These results indicate that at the time of nerve terminal degeneration in the SCG territory a functional depression of the pituitary-thyroid axis takes place, as revealed by the occurrence of low serum TSH and Tt levels and impaired thyroid 131I uptake. The effect of acute SCGx is best explained by both central and peripheral mechanisms rather than by an exclusive central depressive effect on TSH secretion because: (a) exogenous TSH injection did not increase serum T3 levels in SCGx rats; (b) depressed thyroid 131I uptake and serum-free T4 levels, and normal serum TSH concentration were found in SCGx previously subjected to Px.