Although binding by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the Ah receptor is a prerequisite for toxicity, the events responsible for subsequent TCDD effects are essentially unknown. Several lines of evidence have indicated that thyroid hormones share common molecular properties with TCDD and can modulate its toxicity. In the present studies we employed suppression of murine bone marrow hematopoiesis by TCDD as an in vitro model to study the relationship between thyroid hormones and TCDD toxicity. Supraphysiological levels of thyroid hormone mimicked TCDD myelotoxicity, in that both were inhibited by a common antagonist, 1-NH2-3,7,8-trichlorodibenzo-p-dioxin. Furthermore, myelotoxicity by both TCDD and thyroid hormone segregated with the Ah locus in congenic mice. These data provide evidence of a relationship between TCDD and thyroid hormones in that hormonal activity may help regulate TCDD toxicity.