OBJECTIVE: Our objective was to examine changes in CD4⁺ and CD8⁺ cell levels during pregnancy and post partum and to determine whether they differ for human immunodeficiency virus-1–seropositive and seronegative women. STUDY DESIGN: A total of 192 human immunodeficiency virus-1 – seropositive and 148 seronegative women enrolled in a study of mother-to-child transmission of human immunodeficiency virus-1 who had at least two lymphocyte subset measurements performed during pregnancy or post partum were included in this analysis. Mixed effects repeated-measures models were developed to examine changes in CD4⁺ and CD8⁺ cell levels during this period. RESULTS: Consistent with prior reports that CD4⁺ cell levels decline during pregnancy and return to normal post partum, percent levels increased between the third trimester and 12 months post partum among human immunodeficiency virus – seronegative women (1.98%, p = 0.04). However, CD4⁺ levels declined steadily during pregnancy and post partum among seropositive women (−1.57%, p = 0.02 between the third trimester and 12 months post partum; −2.65%, p = 0.0004 between 2 and 24 months post partum). The percent CD8⁺ cell levels increased at or near delivery and declined to baseline between 2 and 6 months post partum in both seronegative and seropositive women, although only the declines were statistically significant in both groups (−2.66%, p = 0.004; and −2.02%, p = 0.02, respectively). CONCLUSIONS: The percent CD4⁺ cell levels declined steadily during pregnancy and post partum among human immunodeficiency virus - seropositive women, indicating that human immunodeficiency virus disease continues to progress during this period. The percent CD8⁺ cell levels increased at or near delivery and declined to baseline post partum in both seronegative and seropositive women. These findings may have important clinical implications for both human immunodeficiency virus - infected and uninfected pregnant women. (AM J OBSTET GYNECOL 1996;174:1461-8.)