We investigated the effects of folate deprivation on plasma folate and homocysteine and its effects on cerebral microvasculature using electron microscopy. Two levels of folic acid (0 mg and 4 mg/kg diet) were fed to 6-mo-old male rats for 8 wk. Dietary folate deprivation decreased plasma folate from 353.0 +/- 29.7 nmol/L to 44.2 +/- 7.2 nmol/L with a concomitant increase in plasma homocysteine from 6.15 +/- 0.9 micro mol/L to 19.5 +/- 2.7 micro mol/L. Plasma folate was negatively correlated with plasma homocysteine at wk 8 (r = -0.876, P = 0.004). Electron microscopic studies of the brains of folate-deprived rats revealed cytoplasmic swelling and mitochondrial degeneration in the endothelium, perivascular amorphous fibrosis and pericytic degenerative appearance in the cerebrocortical microvascular wall. These morphologic changes might be helpful for elucidating the mechanisms underlying the cerebrovascular and neuropathology with folate deficiency.