We conducted a large case-control study to assess the risk of preeclampsia with elevated sTNFp55 concentrations (markers of excessive TNF-alpha release) in Peruvian women. A total of 125 women with preeclampsia and 179 normotensive women were included in a study conducted during the period, June 1997 through January 1998. Antepartum (third-trimester) plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Mean plasma sTNFp55 concentrations were 32.4% higher among preeclampsia cases (920.1+/-30.4 pg/ml) as compared with controls (694.8+/-15.0 pg/ml, Student's t-test P<0.001). There was a strong linear increase in risk of preeclampsia with increasing concentrations of sTNFp55 (linear trend P-value <0. 001). After adjusting for confounding factors, women in the highest quartile experienced a 10-fold increased risk of preeclampsia as compared with women in the lowest quartile (adjusted odds ratio, 10.3; 95% confidence interval, 4.1-25.9). Compared with women in the highest quartile, women in the second and third quartiles experienced a 3-fold or greater increased risk of preeclampsia (adjusted odds ratios were 3.1 and 3.8, respectively). Excessive TNF-alpha release (as measured by the detection of the soluble receptor sTNFp55 in maternal plasma collected before delivery) is increased in pregnancies complicated by preeclampsia as compared with normotensive pregnancies. These findings are consistent with most previous studies.