Objective: Our purpose was to determine whether second-trimester maternal serum β₂-microglobulin levels could be used to predict subsequent development of preeclampsia. Study Design: We first did a cross-sectional study to compare serum concentrations of β₂-microglobulin between women with preeclampsia and normotensive women. Serum β₂-microglobulin concentrations of 11 consecutive patients hospitalized for preeclampsia were compared with those of 11 normotensive women hospitalized for threatened premature labor. The second part of the study consisted of a nested case-control study in which each woman in whom preeclampsia ultimately developed was matched with 2 women who remained normotensive throughout gestation. For that purpose a total of 450 consecutive healthy nulliparous women were studied prospectively. Blood samples were collected between 20 and 24.9 weeks’ gestation and frozen at –20°C until assay after groups had been selected. Results: In the cross-sectional study serum β₂-microglobulin levels were significantly higher in women with preeclampsia than in control women (1.87 ± 0.36 mg/L vs 1.01 ± 0.12 mg/L; t = 7.61; P <.0001). Among the 450 women who were followed up prospectively, preeclampsia developed in 7 (1.5 %). Fourteen of the women who remained normotensive were matched with the 7 women in whom preeclampsia ultimately developed. No difference was found in early serum β₂-microglobulin concentrations between women in whom preeclampsia subsequently developed and those who remained normotensive throughout gestation (1.02 ± 0.12 vs 0.95 ± 0.12 mg/L). Conclusions: Serum β₂-microglobulin levels do not predict subsequent preeclampsia. (Am J Obstet Gynecol 2000;182:595-8.)