Extensive histological and immunohistochemical studies were performed to 
elucidate the histopathogenesis of exencephaly induced in chick embryo as an 
experimental model. The findings were compared with those identified in a chick 
myeloschisis experimental model and in human autopsy cases. The experimental 
model of exencephaly in chick embryos was developed by induction with various 
teratogens including ethylnitrosourea, salicylate, and phenytoin. None of the 
cases of exencephaly was exposed to a teratogen prior to or within Hamburger and 
Hamilton stage 12 (45 to 49 hours postincubation), when the anterior neuropore 
closes. The process of overgrowth in development of exencephaly was identical to 
that of myeloschisis, and the results suggested neuronal overmaturation in the 
histological and immunohistochemical studies. Although the late-stage 
degenerative change with neovascularization over the exposed neural tissue 
(placode) was more severe in human exencephaly, the present experimental study 
may suggest a possible common embryopathogenesis of dysraphism. Exencephaly 
should be regarded as the most severe form of cranium bifidum, as myeloschisis 
is in spina bifida.