Describes the Centers for Disease Control and Prevention (CDC) response plan for the first locally acquired cases of Zika virus infection in the continental U.S. and Hawaii. The Zika virus is spread to people primarily through the bite of an infected Aedes aegypti or Aedes albopictus mosquito. The response activities outlined in this plan are based on currently available knowledge about Zika virus and its transmission, and these activities may change as more is learned about Zika virus infection. Most of the plan focuses on response activities that would occur after locally acquired Zika virus transmission has been identified. CDC also is committed to responding to travel-associated and sexually transmitted Zika virus infections reported in the U.S. before detection of the first locally transmitted case of Zika virus infection. Figures. This is a print on demand report.