In the rat, the restriction of dietary protein during pregnancy leads to maternal vascular dysfunction (Brawley et al. 2004) and raised blood pressure and endothelial dysfunction in the offspring (Brawley et al. 2003). As the diet is casein based and low in sulphur-containing amino acids, it is usually supplemented with 5 g/kg of methionine (Met). Excessive levels of Met are toxic and can promote homocysteine formation (Clarke & Stansbie, 2001). Thus the relatively high Met to protein ratio in the protein-restricted diet may be important in the maternal effects seen in this model and the subsequent development of endothelial dysfunction in the offspring. The aim of this study was to assess the role of Met in this model. Pregnant Wistar rats were fed either a control (C; 18% casein, n=10), a protein-restricted diet (PR; 9% casein, n=8) or a protein-restricted diet with only 2.5 g/kg of Met (PR-low Met; 9% casein, n=10) throughout gestation from conception. At 120 days of age, small mesenteric arteries (~250 μm) from humanely killed male offspring were dissected and mounted in the wire myograph in physiological salt solution, at 37°C and continually gassed with 95% O₂ and 5% CO₂. Following normalisation, cumulative concentration-response curves were constructed to phenylephrine (PE; 10 nM – 100 μM); angiotensin II (Ang II; 10 pM – 100 nM), the endothelium-dependent vasodilator acetylcholine (ACh; 1 nM – 10 μM) and the β-adrenoceptor agonist isoprenaline (1 nM – 10 μM). Data are presented as mean ± S.E.M. and differences calculated by one-way ANOVA with Bonferroni post-hoc correction for multiple comparisons. Significance was accepted for p<0.05. Vasoconstriction to PE and Ang II did not differ between the three groups (p=ns), with the response to Ang II being significantly less than that to PE. Endothelial function as assessed by ACh was not different between the PR and PR-low Met groups (p=ns) both of which were significantly blunted compared to controls (p<0.05). Isoprenaline-induced vasodilatation was not different between the three groups (p=ns). This study suggests that maternal protein restriction and not high dietary Met is important for the development of endothelial dysfunction in the offspring.