Hyperhomocysteinemia has been identified as a risk factor for venous and arterial thrombosis especially in adult populations. Twenty-eight patients with an initial diagnosis of ischemic stroke and 100 controls, aged <or=18 years, were enrolled in this study. The mean plasma total homocysteine (tHcy) levels in patients and controls were significantly different with values of 8.7+/-3.6 and 7.5+/-2.4 micromol/L, respectively (P=0.01). The plasma tHcy at the 95th percentile was 11.5 micromol/L and patients whose plasma tHcy was above the 95th percentile had an odds ratio of 8.2 (95% confidence interval 1.4-47.2, P=0.02) for developing ischemic stroke. The genetic and acquired factors that could have affected plasma tHcy levels were studied and no differences were found between patients and controls. Factors that were investigated were vitamin B12, red blood cell folate, and serum folate levels as well as methylenetetrahydrofolate reductase C677T polymorphism. It is of note, however, that subjects whose plasma tHcy was above the 95th percentile had significantly lower serum folate levels (P=0.02).