In adult systems, high homocysteine (HoCys) levels inhibit methylation reactions and can induce apoptosis in the central nervous system. In embryos, exogenous HoCys is teratogenic and is associated with neural tube defects. Because, methylation inhibitors and inducers of apoptosis can influence membrane composition, we have studied whether or not embryonic exposure to HoCys influenced membrane phospholipid levels, membrane fatty acid composition, and Caspase-3 activities in embryonic chick brains. Embryonic exposure to HoCys caused reduced brain phosphatidylcholine levels and increased levels of brain phosphatidylethanolamine. Exogenous HoCys also promoted decreased levels of long-chain, unsaturated membrane fatty acids and increased levels of saturated short-chain membrane fatty acids. These HoCys-induced brain membrane changes correlated with HoCys-induced increases in brain Caspase-3 activities, HoCysinduced reductions in brain mass, HoCys-induced reductions in embryo mass, and HoCys-induced reductions in the percentage of embryos that survived to 11 days of development (theoretical stage 37). Thus, HoCys-induced changes in brain membrane composition correlated with HoCys-induced apoptosis and reduced embryo viability. ᮊ