We sought to examine the relationship between excessive tumor necrosis factor-alpha (TNF-alpha) release (as measured by sTNFp55 plasma concentrations) and risk of eclampsia and preeclampsia, respectively, among sub-Saharan African women delivering at Harare Maternity Hospital, Zimbabwe. In total, 33 pregnant women with eclampsia, 138 women with preeclampsia and 185 normotensive women were included in a case-control study conducted during the period, June 1995 through April 1996. Postpartum plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Women with eclampsia had significantly higher sTNFp55 than normotensive controls (1.87 vs 1.35 ng/ml, P<0.001). Similarly, women with preeclampsia had sTNFp55 concentrations higher than normotensive controls (1.69 vs 1.35 ng/ml, P < 0.001). The odds ratio for eclampsia was 5.00 (adjusted odds ratio (OR) 5.00, 95% confidence interval (CI) 1.20-20.92) among women in the highest quartile of the control sTNFp55 distribution compared with women in the lowest quartile. The corresponding odds ratio and 95% CI for preeclampsia was 2.37 (1.11-5.06). Postpartum plasma sTNFp55 concentrations are increased among Zimbabwean women with eclampsia and preeclampsia as compared with their normotensive counterparts. These findings are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia/eclampsia. Additional work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy; and to assess whether measurements of sTNFp55 early in pregnancy may be used to identify women likely to benefit from anti-inflammatory therapy.