A woman with pemphigus vulgaris was treated by plasma exchange. Four separate exchanges of approximately 4,000 ml each were performed over a 2-week period. The patient's pemphigus antibody titer decreased from 1/320 before the first exchange to 1/20 after the final exchange, and no new lesions developed for 3 weeks following treatment. It is likely that treatment with plasma exchange helped induce clinical and laboratory remission. The fall in pemphigus antibody titer correlated to loss of acantholytic activity of plasma in vitro. Acantholysis developed in cultures of normal human skin and preexchange plasma but was undetectable in culture of human skin and preexchange plasma diluted to postexchange pemphigus antibody titer. Plasma exchange is a rational approach to management of severe pemphigus but is not practical for routine management.