The activity of phospholipase C (PLC) which hydrolyzes exogenous phosphatidylinositol (PI), was investigated in samples prepared from postmortem normal human brains and Alzheimer disease brains. The enzyme activity did not change significantly after rat brains were left for 24 h at room temperature. The PI-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in Alzheimer's disease.