OBJECTIVE: Recent studies have demonstrated that stimulating autoantibodies against the angiotensin II type 1 receptor (AT1R-AA) are frequently detected in the sera from women with preeclampsia, suggesting that they may play an important role in the pathogenesis of this disease. Nevertheless, the real clinical significance of AT1R-AA in preeclampsia is still controversial due to the paucity of appropriate large comparative studies that require cumbersome, time-consuming, and expensive bioassays to detect AT1R-AA. At present, the prevalence of AT1R-AA in large populations of preeclamptic women is unknown. In an attempt to clarify this issue, we assessed the presence and potential clinical significance of AT1R-AA in a large population of Mexican-Mestizo women with preeclampsia. METHODS: Using a cross-sectional design, we determined the presence of AT1R-AA in 525 pregnant women (99 healthy pregnant, 96 with mild preeclampsia, and 330 with severe preeclampsia) by a new bioassay that employs human embryonic kidney-293 cells stably expressing the recombinant rat AT1R and a 4x nuclear factor of activated T cells responsive luciferase construct as well as by the reference assay in Chinese hamster ovary (CHO) cells. RESULTS: We found that IgG obtained from sera of healthy pregnant women and patients with preeclampsia were unable to induce luciferase activity in both HEK-293 and Chinese hamster ovary cells expressing functional angiotensin II receptor type 1. Therefore, the frequency of patients with AT1R-AA was zero. CONCLUSION: We concluded that in Mexican-Mestizo women agonistic AT1R-AA cannot be invoked as a factor involved in the pathogenesis of preeclampsia. Whether these findings can be attributed to genetic or environmental factors remains unknown.