The generation and monitoring of chemiluminescence (CL) was reviewed and its usefulness to understanding the mechanisms of cytotoxicity was delineated. Cellular CL resulted from the stimulation of membrane receptors of phagocytes by either particles or certain soluble stimulants. This receptor binding causes transmembrane ionic movements with subsequent depolarization of the membrane potential. A variety of cellular biochemical events results then in the activation of the respiratory burst, lysosomal enzyme release, lipid metabolism, and phagocytosis. Phagocytes are also stimulated by ionophores for calcium or sodium ions which do not bind to receptors but induce ionic currents which directly depolarize the cells. By measuring the generation of cellular CL this general activation of phagocytic activity can also be monitored. Two basic approaches exist for following cellular CL: a single well, temperature controlled detector which can be used to follow CL or a sample switching single well, temperature controlled detector which can follow CL from a number of samples. Such measurements have been used to investigate mechanisms by which phagocytic cells are affected by either stimulants or inhibitors, as an assay system to study various disease states, and as an assay system to determine toxicity of environmental or occupational agents on phagocytic cells.