Environmental cues are known to be important in the migration, survival, and differentiation of neural crest cells and their derivatives. Retinoic acid (RA) can increase the number of adrenergic cells that develop in neural crest cultures in a dose dependent manner. These results with RA prompted us to investigate the effects of other retinoids and other related compounds on neural crest cultures. We have investigated the role of thyroid hormone (T3) in the development of adrenergic cells in quail neural crest cultures. T3 produced a significant decrease in the number of catecholamine-positive cells that developed in neural crest cultures after 7 days in vitro, as compared to untreated controls. The decrease in adrenergic cells produced by T3 was paralleled by a decrease in the number of tyrosine hydroxylase-positive cells, but T3 did not reduce either total or melanocyte cell number. Cultures were sensitive to T3 during the first 5 days in culture and T3 was not cytotoxic to adrenergic cells. The decrease in adrenergic cells seen with T3 was partially reversed by RA suggesting that these two compounds may be working through a common pathway.