An unprecedented outbreak of fatal eastern equine encephalitis (EEE) virus occurred during the late summer and fall of 1984 in endangered whooping cranes (Grus americana) at the Patuxent Wildlife Research Center, Laurel, Maryland. As part of efforts to prevent future epizootics of EEE. studies were conducted to evaluate the antibody response of cranes following vaccination with a formalin-inactivated EEE virus vaccine. Viral specific neutralizing antibody was elicited in sandhill cranes (Grus canadensis) and whooping cranes following 1M inoculation with the vaccine. Among the 1M-inoculated cranes, peak antibody titers of 1:80 on days 30 to 60 had waned to undetectable levels by days 90 to 120. Although the initial titers were not increased by the first booster dose, the duration of the antibody was extended considerably. Whooping cranes, receiving vaccine 6 months after their first vaccination, developed titers of 1:80 to 1:320 by day 30. At 45 days after the final vaccination, these titers had dropped to 1:10 to 1:160. Cranes with preexisting EEE virus antibody, apparently reflecting natural infection, exhibited an anamnestic response indicated by a rapid increase and sustained high antibody titer. Even though EEE virus vaccine induced neutralizing antibody and produced no adverse side effects, further studies will be required to assess the significance of this response as a strategy for protecting whooping cranes against natural EEE virus infection. The loss of captive whooping cranes to the EEE virus presented a previously unrecognized risk and obstacle to recovery of this species. Not only was, there a setback in the captive breeding and reintroduction program for the whooping crane, but, because of the susceptibility of the species to the EEE virus. establishment of additional crane populations may be more complicated than initially envisioned. However, through continued surveillance, serological monitoring, and vaccination activities, we are confident that the impact of EEE virus on whooping crane recovery can be overcome to the ultimate benefit of this endangered species.