To estimate and to prevent the developmental brain damage caused by maternal environmental agents, the results were compared between epidemiological and experimental studies. I. Ethanol. The features of CNS involvement in human FAS (fetal alcohol syndrome) and FAE (fetal alcohol effects) were developmental delay and intellectual impairment. In rat FAS or FAE, a beneficial effect of supplementary zinc on the fetal cerebrum was observed, but was limited. The consistent dysformation of synapses during early brain development may be associated with the functional impairment of CNS in FAS and FAE. II. Caffeine. A reduction in the fetal cerebral weight was observed with caffeine ingestion during pregnancy at levels of 1.5-3.0μg caffeine/ml or g wet wt. in dams and fetuses. Maternal caffeine disturbs the neonatal cerebrum and produces behavioral abnormalities in developing rats. III. X-irradiation. Our study provides evidence of the protection by vitamin E of neuronal development in X-irradiated rat fetuses, through its antioxidant properties, against attacks by free radicals and/or lipid peroxide. IV. Low copper level in brain. A teratogenic effect of triethylene tetramine dihydrochloride, a chelating drug for copper, on the mouse brain was noted, both grossly and microscopically, with a dose of higher than 6, 000 mg/l, which is twenty times as high as the clinical treatment dose. V. Tobacco. Thirty- three percent of human FTS (fetal tobacco syndrome) cases had CNS involvement, which was characterized by developmental delay. Fifty percent or more of FTS children of women who smoked more than 20 cigarettes per day had CNS involvement. In conclusion, the concomitant effects of maternal enviromental agents on human brain development should be studied.