The effects of restraint stress on the distribution of lymphocyte subsets were studied in young BALB/c male mice. Loss of whole body weight, a reduction in the weights of spleen and lymph nodes, and higher levels of serum corticoste-rone were evident after a single continuous restraint period of 16–18 h. Tissue sections of spleens from restrained animals revealed erythrocyte depletion in the contracted red pulp. Furthermore, there was a significantly higher proportion of CD4+, but not of CD8+, lymphocytes in the spleen. The proportion of the CD4+ subset was markedly diminished in peripheral blood, whereas no changes were detected in lymph nodes. Restraint resulted in enhanced allogeneic mixed lymphocyte reactivity and in altered expression of some CD4+, but not CD8+, splenocyte adhesion molecules (CD44, LFA-1 and VLA-4). Removal of circulating corticosteroids by surgical adrenalectomy abolished the restraint-induced changes in lymphocyte adhesion molecule expression. The findings suggest that the observed differences in lymphocyte subset distribution of lymphoid organs may be due to changes in the pattern of adhesion molecule expression.