Efficacy of a poly-gamma-D-glutamic acid anthrax capsule vaccine was assessed in a mouse model of infection. Capsule by itself was protective against lethal challenge with a toxin(-), capsule(+) Bacillus anthracis strain. Conjugation of capsule to bovine serum albumin resulted in enhanced IgG anti-capsule antibodies measured by ELISA, but completely abrogated the protection. The protective unconjugated capsule vaccine elicited significantly higher IgM titers and opsonic activity than did the non-protective capsule conjugate. When tested against a fully virulent toxin(+), capsule(+) B. anthracis strain, neither capsule nor protective antigen alone was protective. However, the combination of the two protected against a lethal challenge. These results suggest that capsule may enhance the protection afforded by protective antigen vaccines against anthrax if opsonizing antibodies are produced. Surprisingly, some protection was also observed when protective antigen was conjugated to itself.