Group B Streptococcus (GBS) beta C protein elicits protective antibodies in experimental animals, making beta C protein an attractive component of a human GBS glycoconjugate vaccine. We determined whether natural exposure to beta C protein elicits antibodies in humans. Geometric mean concentrations (in micrograms per milliliter) of beta C-specific immunoglobulin (Ig) M and IgG as determined by enzyme-linked immunosorbent assay were similar in serum from 16 colonized (0.82 and 0.76, respectively) and 48 age-matched noncolonized (0.96 and 0.74, respectively) pregnant women. Serum from 3 women with beta C GBS bacteremia had significantly higher levels of IgM (6.0) and IgG (52.9) (P=.01 and 0.01, respectively). Invasive disease but not colonization elicits beta C-specific IgM and IgG.