The globule leucocyte is a cell with a wide distribution in the digestive, respiratory, biliary, urinary and genital tract epithelia of homeotherms. It occurs in the crypts of the rat small intestine and within the epithelium on the villous bases but not on the remainder of the villi. A characteristic feature of this cell is the presence of acidophilic cytoplasmic granules, 0.5 to a few micrometers in diameter. The nucleus resembles that of intraepithelial intestinal lymphocytes. In this investigation, a quantitative study was made of the effect of thyroidectomy and/or castration on the number of globule leucocytes in the duodenal crypts of immature and adult rats. In sham-operated rats, globule leucocytes were rare, occurring with a frequency of 1 or 2 per 1,000 epithelial cells. After thyroidectomy, they increased to 14--20 per 1,000 epithelial cells. Castration did not influence the number of globule leucocytes but resulted in an increase in the number, size and acidophilia of their cytoplasmic granules. In immature rats, but not in adults, castration combined with thyroidectomy enhanced the effect of thyroidectomy, increasing globule leucocyte number to 32 per 1,000 epithelial cells. Treatment of thyroidectomized-castrates with thyroxine, initiated 38 days after operation, reduced the crypt globule leucocyte population to normal, whereas treatment with testosterone did not. Growth hormone failed to influence the elevated number of globule leucocytes in thyroidectomized rats, suggesting that this action of thyroxine was not mediated via an influence on growth hormone release. Because of their similar nuclear morphology, intraepithelial crypt lymphocytes were also counted and there was no obvious relationship in the fluctuations of these two cell populations. It is suggested that the greater number of crypt globule leucocytes in thyroid deficiency may reflect changes in the intestinal secretory immunoglobulin system and this is being investigated, beginning with a study of the distribution of IgE.