Problem The aim of this study was to evaluate how fetal monocyte activation and maternal anti-fetal antigen-specific antibody-secreting cells (ASC) affect the severity of hypertensive disorder complicating pregnancy (HDCP). Method of study Forty-six healthy third-trimester pregnant women and 20 patients with gestational hypertension, 20 with mild pre-ecalmpsia and another 20 with severe pre-eclampsia were included in the study. Interleukin-6 (IL-6) release from cord blood monocytes was examined by intracellular cytokine staining and flow cytometric analysis. Moreover, the maternal anti-fetal antigen-specific ASC were detected by enzyme-linked immunospot assay. Results A significantly increased percentage of IL-6-positive monocytes were detected in the cord blood of study groups compared with the controls (P < 0.01). The percentage of IL-6-positive monocytes was increased as the disease progressed (P < 0.05). There were more anti-fetal antigen-specific ASC in the study groups than those in the controls (P < 0.001). Furthermore, the anti-fetal antigen-specific ASC showed difference in gestational hypertensive and severe pre-eclamptic groups (P < 0.05). Conclusion We conclude that the fetal monocyte activation and the increase in maternal anti-fetal antigen-specific ASC were related to the incidence and severity of HDCP. These results provide both indirect and direct evidence for the occurrence of exaggerated maternal humoral immunity against the fetal antigens in HDCP.