The effect of T4 on specific PRL binding in the kidneys and adrenals was measured in intact, hypophysectomized, and thyroidectomized male rats. PRL binding in the kidneys was reduced from 12.1 +/- 1.1% in the intact group to 4.5 +/- 0.5% after hypophysectomy; 4-day replacement with T4 returned PRL binding to intact values. T4 administered to intact rats significantly increased PRL binding above intact values. Thyroidectomy reduced PRL binding in the kidneys from 14.9 +/- 1.2% to 7.0 +/- 0.6%, and T4 treatment restored PRL binding to intact values. PRL binding was measured at 2, 3, 5, 7, and 10 days after thyroidectomy in kidneys and found to decrease progressively from 8.2+/-0.5% in the intact rats to 2.3+/-0.3% on day 10. A single injection of T4 doubled PRL recetor binding in kidneys of thyroidectomized rats at 12 h and returned binding to intact levels at 24 h. In contrast to the effects of T4 on kidney PRL binding, adrenal PRL binding was only slightly altered by thyroidectomy and T4. These results suggest that T4 has a specific role in regulating PRL receptors in the kidneys but not in the adrenals. Since PRL receptors in the adrenals were only slightly altered by thyroid status, it is believed that the changes in kidney receptors represent a specific rather than a general metabolic effect of T4.