A quantitative approach was developed to classify Holstein cows and heifers based on phenotypic variation of serum antibody response and to determine associations with peripartum mastitis. Using an index, 136 cows and heifers were classified into high (Group 1), average (Group 2), or low (Group 3) antibody groups following immunization with ovalbumin at wk -8, -3, and 0 relative to parturition. The ranking of groups based on the quantitative index of serum antibody response to ovalbumin were similar for sera and whey antibody such that Group 1 > Group 2 > Group 3. Animals were also vaccinated with Escherichia coli J5 (Rhône Mérieux, Lenexa, KS) at wk -8 and -3 relative to parturition. The ranking of groups for E. coli J5 was similar to that observed for serum and whey antibody to ovalbumin. Serum and whey IgG1 and IgG2 concentrations were measured at wk 0, 3, and 6 but differences between groups were not significant. There was no occurrence of mastitis for Group 1 animals in two of the herds. In contrast, Group 1 animals from the third herd had the highest occurrence of mastitis; however, these cases all occurred in first-parity heifers. According to pooled data across all herds, Group 3 animals had the highest occurrence of mastitis. Heritability estimates of serum antibody response to ovalbumin varied between 0.32 to 0.64 depending on week relative to parturition. Heritability estimates of serum antibody response to E. coli J5 also varied between 0.13 to 0.88 depending upon week relative to parturition. These results indicate that high peripartum antibody may be beneficial in some herds.