The fact that the reversion of CD28 took place rapidly (between 24 and 48 h of stimulation) favours the interpretation that in B-CLL patients the prolonged downregulation of the surface CD28 molecule may result from enhanced ligation-stimulated CD28 receptor endocytosis, and/or disturbed recycling to the cell surface or increased proteolytic intracellular degradation. This evidence concerns the gene CD28 and B-cell chronic lymphocytic leukemia.