Pregnancy is associated with modifications in the maternal immune system that may be involved in the absence of rejection of the fetoplacental graft characterized by the presence of paternal antigens. This active and specific tolerance towards the fetoplacental unit seems to be compromised in pregnancy-induced hypertension (PIH). To evaluate whether the immunological state in patients with PIH is altered with respect to normal pregnant women we studied 15 patients with PIH, 15 uncomplicated pregnant and 10 healthy nonpregnant women using monoclonal antibodies directed to specific lymphocyte antigen determinants, cytokines (TNF) and soluble molecules (sIL·2R, sCD8). The percentage of CD4 lymphocytes and of natural killer (NK) cells was significantly higher in PIH patients compared to controls (CD4: 42.9 ± 10.5 vs. 32.7 ± 12.5%; p < 0.05; NK: 14.7 ± 6.3 vs. 8.3 ± 3.4%; p < 0.01). However, these values did not differ when compared to normotensive nonpregnant controls (CD4: 53.1 ± 5.9%; NK: 17.2 ± 7.1%). In addition, the soluble IL·2 receptor (sIL-2R) was higher in PIH patients when compared to control patients (725.5 ± 194.2 vs. 482.5 ± 187.2 U/ml; p < 0.01). The immune response observed in normal pregnancies responsible for the tolerance towards the fetoplacental unit seems to be altered in PIH patients as suggested by higher levels of CD4 and NK cells, and sIL-2R. This may lead to a chronic rejection syndrome and be involved in the pathophysiology of PIH.