Millions of people consume betel nut for increased capacity of work. It contains arecoline which is highly toxic and has several untoward side effects on endocrine functions. In this article, the role of arecoline on thyroid function under metabolic stress was investigated in mice. Water or food-deprivation, each for 5 days, caused ultrastructural degeneration of thyro-follicular cells, evident from pycnotic nuclei, scanty rough endoplasmic reticulum and mitochondria followed by depletion of blood serum T-3 and T-4 levels with alteration of TSH level as compared with control. Thyroid activity was also suppressed ultrastructurally as well as at hormonal level after arecoline administration. Further, arecoline treatment in water deprivation or food deprivation stress also caused thyroid dysfunction beyond that of metabolic stress, as evident from further ultrastructural degeneration of thyrocytes and depletion of thyroid hormones in mice. The findings suggest that arecoline aggravates hypothyroid condition in metabolic stress in mice.