BACKGROUND Moderate hyperhomocysteinemia is an independent risk factor for stroke. The relationship between homocysteinemia and stroke and its related factors are unknown in Spain. METHODS We determined plasma homocysteine concentrations in 80 stroke patients and in 48 control subjects without vascular risk factors. Folate, vitamin B12 and creatinine concentrations were also measured in stroke patients. RESULTS Total plasma homocysteine concentrations were higher in stroke patients compared to controls (11.2 [SD 3.2] mumol/l versus 8.1 [2.6] mumol/l; p < 0.001). Hyperhomocysteinemia was present in 20% of patients and in 2.2% of controls (odds ratio [OR] = 5.75; 95% CI = 1.24-53.4; p < 0.01). Homocysteine values were related to vitamin B12 (r = 0.28; p < 0.05) and creatinine concentrations (r = 0.24; p < 0.05). Multiple regression analysis showed that about 15% of the variation in plasma homocysteine concentrations could be predicted by the values of vitamin B12 (p < 0.001) and creatinine (p < 0.05). Homocysteine values were unrelated to age, sex, folate concentrations, atherosclerotic subtype or to the presence of vascular risk factors. CONCLUSIONS Moderate hyperhomocysteinemia was present in about 20% of stroke patients in our series. Homocysteine plasma level was not related with other stroke risk factors or with the atherosclerotic subtype of stroke, but it was partially related with the renal function parameters and the serum levels of vitamin B12.