A protein microarray containing 144 known or putative virulence-related proteins of Yersinia pestis was used to evaluate the antibody responses of plague patients. Forty-two proteins were found to be expressed in vivo and antibodies against 14 of them were detected in all patients analyzed, providing potential candidates for novel protective antigens and novel serodiagnostic markers in Y. pestis. Moreover, the lack of antibody to LcrV in the five patients in Focus F might be a challenge to our understanding of the pathogenesis of Y. pestis.