Using 31P-NMR spectroscopy, we have investigated possible involvement of metabolic processes in the lysis of nucleated cells induced by low levels of antibody to cell surface antigens and complement. Within 10 min of antibody plus complement attack, before onset of overt lysis, we have observed a marked, selective reduction in the intracellular content of phosphocreatine and adenosine triphosphate (ATP). A longer attack is accompanied by total depletion of either phosphocreatine or ATP in residual cells which preserved other phosphate compounds. The results indicate that in nucleated cells formation of putative complement-dependent membrane channels induces exhaustive hydrolysis of ATP. It is suggested that ATP deprivation could in turn lead to colloid-osmotic swelling, membrane rupture, and cell death.