A phospholipase C activity highly specific for lysophosphoinositide (lysoPI-PLC) has been demonstrated to be present in synaptic plasma membranes of the rat brain. Several lines of evidence suggested that the lysoPI-PLC is an enzyme distinct from known isoforms of phosphoinositide-specific phospholipase C (PI-PLC). On the other hand, the occurrence of a Ca(2+)-independent phospholipase A1 hydrolyzing PI in rat brain was also demonstrated. The lysoPI-PLC hydrolyzed the 2-acyl isomer as well as the 1-acyl isomer of lysoPI. These findings suggest possible pathways for PI metabolism through lysoPI to yield monoacylglycerol (mainly 2-arachidonoyl glycerol) and inositolphosphates in the brain, which are different from the well-characterized PI-PLC pathway.