The possible influence of 48 hr of sleep deprivation on in vitro DNA synthesis of blood lymphocytes and on the adhesiveness and intracellular, stainable activity of alkaline phosphatase in blood granulocytes was studied in twelve young male volunteers. Following the sleep deprivation, all 12 subjects showed marked reductions of DNA synthesis after stimulation with phytohemagglutinin. Pre-exposure levels were regained 5 days after terminating the vigil. No changes were noted in granulocyte adherence or alkaline phosphatase activity. The results suggest that sleep deprivation may decrease cell-mediated immune reactions and thereby impair some aspects of host defense.