Pre-eclampsia is characterised by hypertension, proteinuria, oedema (including cerebral oedema) and placental under-perfusion, attributed to reduced angiogenesis in the placenta. Vascular Endothelial Growth Factor (VEGF) is upregulated in serum and plasma from pre-eclamptic patients. There are two families of VEGF produced by alternative splicing; an angiogenic family, which causes vasodilatation and increased permeability, and an inhibitory family that inhibits blood vessel growth and vasodilatation. The isoform type of VEGF that is upregulated in pre-eclampsia is unknown, so we tested the hypothesis that high VEGF levels in pre-eclampsia are inhibitory VEGF isoforms. Placentae were collected from 21 pregnant women aged 18-37 from Gloucester Royal Hospital and Southmead Hospital, Bristol, UK. The protocol for this study was approved by the local Ethical Committee and informed consent obtained from all patients. 8 subjects were diagnosed with pre-eclamptic toxaemia, defined as systolic blood pressure above 140 mmHg and diastolic pressure above 90 mmHg, proteinuria (>1000mg per 24h collection) with resolution of both hypertension and proteinuria by 12 weeks postpartum. Samples from healthy, normotensive pregnant women were taken at term and included as controls. Protein was extracted from the placentae, quantified and subjected to Western blotting and ELISA using an antibody that detects all isoforms of VEGF (pan-VEGF), and one that is specific to the anti-angiogenic family-VEGF_xxxb. VEGF_xxx levels were calculated as the difference between total VEGF and VEGF_xxxb. Western blots probed with a pan VEGF antibody showed strong staining of bands at approximately 28, 38 and 44 kDa, corresponding to dimers of VEGF₁₂₁,VEGF₁₆₅ and VEGF₁₈₉. When blots were probed with antibodies to VEGF_xxxb, the same pattern was seen in all samples, with bands at 38 and 44 kDa showing up strongly, and 28 kDa clear, but less strong. ELISA of the protein showed lower expression of VEGF_xxx in normal (0.97±0.19ng/mg) than pre-eclamptic (1.67±0.32ng/mg, p=0.06) placentae. VEGF_xxxb expression however was lower in pre-eclamptic (7.1±0.8pg/ml) than in normal samples (11±1.3pg/ml, p<0.05, Mann Whitney U test). The mean percentage of total VEGF that was VEGF₁₆₅b decreased from 1.48±0.24% in normal placentae to 0.66±0.2% in pre-eclamptic patients (p<0.05). In summary VEGF_xxxb is downregulated in pre-eclampsia. It makes up a very small proportion of total VEGF in placenta unlike in other tissues so far investigated (e.g prostate, colon and vitreous)and is therefore unlikely to contribute to the symptoms of pre-eclampsia. VEGF_xxxb downregulation is probably rather a sequelae of tissue underperfusion in the placenta.