Recently, a family-based association analysis showed that the haplotype carrying a low expression of the variant CD3Z 844 T>A (rs1052231) polymorphism located in the 3'-untranslated region of CD3Z predisposes to systemic lupus erythematosus (SLE) incidence. We analyzed the prevalence of the CD3Z 844 T>A polymorphism in SLE patients (n = 152) and controls (n = 304) in Poland. We observed that women with the CD3Z AA and CD3Z AT genotypes exhibited a 1.845-fold increased risk of SLE [95% confidence intervals (95% CI) = 1.222-2.787, P = 0.0038]. However, we did not find an increased risk for the homozygous CD3Z AA genotype (odds ratio = 1.204, 95% CI = 0.2838-5.108, P = 1.0000). This observation confers that genetic factors causing a decreased level of CD3-zeta in T cells may predispose to SLE incidence.