We investigated the relations between plasma concentrations of homocysteine and vitamins B-12 and B-6 and folate, and scores from a battery of cognitive tests for 70 male subjects, aged 54-81 y, in the Normative Aging Study. Lower concentrations of vitamin B-12 (P=0.04) and folate (P=0.003) and higher concentrations of homocysteine (P=0.0009 ) were associated with poorer spatial copying skills. Plasma homocysteine was a stronger predictor of spatial copying performance than either vitamin B-12 or folate. The association of homocysteine with spatial copying performance was not explained by clinical diagnoses of vascular disease. Higher concentrations of vitamin B-6 were related to better performance on two measures of memory (P=0.03 and P=0.05). The results suggest that vitamins (and homocysteine) may have differential effects on cognitive abilities. Individual vitamins and homocysteine should be explored further as determinants of patterns of cognitive impairment.