Recent studies show that several cell types which mobilize intracellular Ca++ in response to hormones or neurotransmitters also hydrolyze phosphatidylinositol 4,5 biphosphate to produce diacylglycerol and a water soluble molecule inositol trisphosphate (InsP3) which may mediate mobilization of intracellular Ca++. In the present study we investigated in rat brain microsomes the possible involvement of InsP3 in Ca2+ mobilization. ATP dependent accumulation of calcium was observed in the brain microsomes and InsP3 caused a rapid release of calcium which was followed by a slow re-uptake. The two organelles thought to be responsible for calcium storage are endoplasmic reticulum and mitochondria. We found that InsP3- induced Ca++ release was not observed in mitochondria. Moreover, the presence of mitochondrial inhibitors, oligomycin and sodium azide, during calcium uptake, did not affect the ability of Ins3 to release Ca++ from the microsomes. In addition, electron microscopy did not reveal mitochondria in the microsomal fraction. Brain microsome may provide a model for investigating the effects of ethanol on regulation of Ca++ mobilization in the central nervous system. We are continuing the studies using sand dollar eggs as an experimental model, for investigating the mechanism of the effects of ethanol on the early stages of development.