Both perchlorate and arsenate are environmental contaminants. Perchlorate is a definitive thyroid disruptor, and arsenic may disrupt thyroid homeostasis via multiple pathways. To evaluate the effects of sodium perchlorate and sodium arsenate on thyroid function and possible interactions between them, zebrafish (Danio rerio) were exposed to sodium perchlorate (10 and 100 mg/L), sodium arsenate (1 and 10 mg/L), and the mixture sodium perchlorate + sodium arsenate (10 + 1 and 100 + 10 mg/ L) for up to 90 days. At day 10, 30, 60, and 90, fish were sampled and analyzed forthyroid histopathological end points including follicular cell height, follicle size, colloid size, colloid depletion, hyperplasia, and angiogenesis. Effects on epithelial cell height (hypertrophy) were seen as early as 10 days after exposure. Perchlorate induced changes in all parameters staring at 30 days of exposure. Prolonged perchlorate exposure induced angiogenesis, a relatively new marker of thyroid disruption. Sodium arsenate was less effective than sodium perchlorate in causing thyroid histopathologies, but transient responses were seen for hypertrophy, hyperplasia, and colloid depletion (% colloid). This is the first report of arsenate-induced effects on thyroid histopathology. However, because statistically significant effects were not consistently seen in all end points, evidence for arsenate as a thyroid disruptor remains equivocal. In general, the sensitivity of the following histopathological indicators for indicating thyroid perturbations is, in descending order: follicular cell height > percent of colloid area/follicle area > colloid area/follicular cell height > hyperplasia > angiogenesis > colloid area >follicle area = fish growth.