Abstract A guinea pig model was developed to determine whether humoral immune responsiveness is altered during pregnancy. Pregnant animals were immunised at mid-gestation with haptenated protein. The humoral response to antigen was measured as numbers of antibody-producing cells in the spleen, the affinity of the antibody produced by spleen cells and the levels of IgG in the serum. The values obtained were compared with those from an age matched non-pregnant control group. Early in the primary response, there was a significant decrease in the number of IgM antibody-producing cells with an associated decrease in serum IgM levels in pregnant animals. Late in the primary response, pregnant and control animals had similar levels of IgM antibody-producing cells. During the later stages of the response, many of the pregnant animals did not respond with IgG antibody-producing cells or IgG in the serum. When IgG-producing cells were detected, the antibody was of lower affinity than that observed with the control group. A selective lack of responsiveness was detected in the primary response of pregnant guinea pigs. The reduced number of IgG antibody-producing cells in gravid animals suggests that an immune switch from IgM to IgG is impaired in pregnancy. The low affinity of antibody produced indicates the immunoglobulin produced in pregnancy may also be functionally limited.