The stimulatory effects of ascorbate on neutrophil motility in vitro and in vivo and lymphocyte transformation to mitogens following ingestion or intravenous injection of ascorbate have been found to be related entirely to inhibition of the autooxidative effect of the myeloperoxidase/hydrogen peroxide/halide system (MPO/H2O2/halide system). Stimulation of neutrophil migration and lymphocyte transformation following a single intravenous injection of 1 g of ascorbate was associated with inhibition of the MPO/H2O2/halide system. The immunostimulatory activity and peroxidase inhibitory activity was related entirely to the serum ascorbate level. The relationship between inhibition of the peroxidase/h2O2/halide system and stimulation of neutrophil motility and lymphocyte mitogen-induced transformation was further established by using the horseradish peroxidase (HRP)/H2O2/halide system in vitro. Neutrophils and lymphocytes, exposed to this system, manifested markedly impaired chemotactic responsiveness and mitogen-induced transformation, respectively. However inclusion of ascorbate with the peroxidative system protected the neutrophils and lymphocytes from these inhibitory effects. Further studies in 3 patients with chronic granulomatous disease (CGD) and 10 patients with bronchial asthma suggested that ascorbate may be of value to improve the primary immunological abnormalities (neutrophil motility and antimicrobial activity) in CGD and the secondary abnormalities (neutrophil motility and lymphocyte transformation) found in some individuals with bronchial asthma.