Regional levels of cerebral inositol-1-phosphate (Ins1P), an intermediate in phosphoinositide (PI) cycle, were readily detected with a new gas chromatographic (GC) method. GC analysis of trimethylsilyated Ins1P and myo-inositol-2-phosphate with a fused silica capillary SE-30 column and flame ionization detection was linear at picomolar range (pmol/microliter) with a sensitivity to a level of 2 pmol. Also, inositol monophosphates and glucose-6-phosphate are separated in unstimulated brain tissue. The mean recovery of the method is 98 +/- 5.2%. Ins1P levels were higher in frontal than in caudal regions in control brains. Lithium treatment increased the levels of Ins1P throughout the brain but mostly in frontal brain regions and in the hippocampus. The present GC assay to measure the accumulation of Ins1P, an index for the activity of PI signaling, may be suitable for exploring regional differences in cerebral receptor-coupled PI signalling in vivo.