Thymic atrophy and lymphopenia are immunological hallmarks of many forms of malnutrition including deficiencies in zinc. Extreme thymic atrophy (70-80%) along with a 50% loss of splenocytes in mice maintained on a zinc deficient diet (ZD) for 30 days suggested that the deficiency might be altering lymphopoiesis or the production of new lymphocytes by the bone marrow. As shown herein, mice who were marginally zinc deficient being 72-75% the body weight of adequately fed controls, exhibited a 50% decline in pre B-cells and a 25% decline in immature B-cells. The mature B-cells of the marrow appeared fairly resistant to effects of suboptimal zinc intake. Interesting, this pattern was similar to results obtained by treating bone marrow cells with levels of glucocorticoids analogous to those found in nutritionally deficient rodents. Furthermore, these same concentrations of steroids were shown to induce significant levels of apoptosis or cell death among pre and immature B-cells which accounted for their declining numbers subsequent to exposure to glucocorticoid. In order to better ascertain the potential role of glucocorticoids generated during zinc deficiency on lymphopoietic processes, adrenalectomies were performed in an attempt to remove glucocorticoids from the equation. Subsequently, adrenalectomized and sham operated mice were placed on a ZD or zinc adequate diet (ZA). Levels of steroids at the time of sacrifice were elevated six fold in non-adrenalectomized ZD mice compared to ZD adrenalectomized mice. Removal of the adrenal gland protected the thymus of ZD mice from atrophy and also provided substantial protection of lymphopoietic processes.(ABSTRACT TRUNCATED AT 250 WORDS)