Membrane-associated functions are profoundly influenced by the fluidity and physical state of the membrane. These two features are in turn determined by the membrane lipid acyl chain profile. Reactive oxygen species (ROS) modify the acyl chains by lipid peroxidation of the unsaturated chains, thus affecting the fluidity and physical state of the membrane. By enhancing endogenous ROS levels, therefore, aging, and disease affect integral membrane function, such as the cell-mediated immune (CMI) reaction involving phagocyte membrane NADPH oxidase. This enzyme relies on triggering by membrane-inserted protein kinase C (PKC), for its superoxide (O2-) producing function. The molecular mechanism of the depressed immunocompetence in the aged, and in disease and malnutrition, may reside in the down-regulation of these two enzymes by excess ROS. These excess ROS arise from activated phagocytes in disease states, and from enhanced ROS from other sources in the aged, as well as from the decrease in antioxidants in the aged. Research should be intensified on PKC and NADPH oxidase function with the aim of unravelling the molecular mechanism of the depressed immunocompetence, and thence, of formulating appropriate intervention strategies against it.