The aim of this study was to investigate the effects of acute, methionine-induced hyperhomocysteinaemia on endothelial function of skin microcirculation in diabetic compared with non-diabetic persons. Endothelial- and non-endothelial-dependent vasodilatation of the skin microcirculation were evaluated in 20 persons with type 2 diabetes (59.95+/-2.36 years old) and 24 age- and gender-matched controls using laser Doppler flowmetry, during fasting and four hours after 0.1 g/kg methionine-induced acute hyperhomocysteinaemia. Methionine loading caused a comparable increase of homocysteine in the two groups. Four hours after induction of acute hyperhomocysteinaemia, endothelial-dependent vasodilatation (acetylcholine effect) was lower in the diabetic patients compared with the controls ([mean+/-SEM] 8.09+/-1.18-fold increase in diabetic patients vs. 11.11+/-1.33-fold increase in controls, p=0.027). The same was observed for the endothelial-independent vasodilatation (sodium-nitroprusside effect, 7.55+/-0.80-fold increase in the diabetic patients vs. 12.19+/-1.26-fold increase in controls, p=0.008). Acute hyperhomocysteinaemia causes a decreased response of both endothelial-dependent and endothelial-independent vasodilatation of the skin microcirculation in diabetic compared with non-diabetic persons. These alterations might contribute to the vascular complications of hyperhomocysteinaemia in diabetes, and especially the microvascular ones.