The aims of this study were: to quantify immunoreactive tumour necrosis factor α (TNF-α) concentrations in maternal plasma and amniotic fluid obtained from women during pregnancy and labour, both at term and preterm; and to establish the effects of bacterial endotoxin and cytokines on the in vitro release of TNF-α from intrauterine tissues. Maternal plasma TNF-α concentrations did not change during pregnancy (457.2 ± 102.9 ng/l, mean ± SEM, N=52) or at the time of labour (543.5 ± 138.6 ng/l, N = 43). In contrast, amniotic fluid TNF-α concentrations increased significantly (p < 0.05) during pregnancy (early pregnancy, EP, 93.0 ± 24.8 ng/l, N = 7; preterm not-in-labour, PNIL, 186.8 ± 42.9 ng/L N=16; term not-in-labour, TNIL, 499.7 ± 150.9ng/l, N=13) and in association with preterm labour (preterm in-labour, PIL, 958.7 ± 575.6ng/l, N = 5 vs PNIL. 186.8 ± 42.9 ng/l, N = 16). Choriodecidual and placental explants (N = 3) maintained in in vitro culture released TNF-α Furthermore, the release of TNF-α was increased significantly (p < 0.05) by bacterial endotoxin (lipopolysaccharide, 10ng/l-10mg/l) but was not affected by the following cytokines at the indicated doses: interleukin-1α (0.28 nmol/l), interleukin-6 (12.5 nmol/l), granulocyte colony-stimulating factor (2.5 nmol/l). granulocyte-macrophage colonystimulating factor (35mnol/1) macrophage colony-stimulating factor (1.2nmol/l), leukaemia inhibitory factor (0.45 nmol/l) and transforming growth factor-β (0.4nmol/l). The data obtained in this study are consistent with a role for TNF-α in bot h preterm labour and normal labour at term.