The effect of homocysteine (HCY) on the development and endocytosis of rat visceral yolk sac (VYS) was investigated. A preliminary method on early (GD9.5) rat yolk-sac placenta cultured in vitro was established by techniques using microdissection and transplantation. The results showed that HCY did damage VYS development and blood vessel formation, the damages were characterized by shrunk surface, small or defective blood island and significant reduction of diameter (P < 0.01). HCY also inhibited the process of VYS transport, specifically the endocytosis (as measured by [U-14C] sucrose uptake), the rate of endocytosis was significantly decreased when HCY was included in the medium (P < 0.01). These results suggested that the inhibition of sanguimotor development and the reduction of endocytosis induced by HCY may directly correlate with the teratologic and embryopathologic events.