Studies of virulence by the human pathogen Bordetella pertussis, the causative agent of whooping cough, has been shown to be controlled by the bvgAS operon. Induction of virulence-related genes only occurs when B. pertussis is grown at 37°C and certain bvgS mutations result in a loss of the temperature response. DNA sequence analysis indicated that the bvgS gene product contains a potential membrane spanning region. In addition, all bvgA mutants incapable of causing virulence had an aspartate residue changed to alanine. Based on this information propose a model for how bvgA and bvgS play a role in B. pertussis virulence.