The phosphoinositide signal transduction system, and particularly, phospholipase Cbeta isozymes, are relevant in the etiopathogeny of human neuropsychiatric pathologies such as depression. Stimulation of phospholipase Cbeta activity by muscarinic receptors and G proteins was determined in crude and synaptosomal membrane preparations from nine postmortem human frontal cortices (postmortem delay range 8 to 50 h). Thus, the phospholipase Cbeta activity was determined by measuring the hydrolysis of exogenous [3H]-phosphatidylinositol 4,5-bisphosphate. There was a postmortem delay-mediated decrease in the PIP2 hydrolysis irrespective of the membrane preparation used (P < 0.05). Moreover, there were statistically significant differences for exponential decay curve parameters (K factor and Span) of PLCbeta activity induced by agonist-mediated activation between crude and synaptosomal membrane preparations. These results show that the postsynaptic component of the PLCbeta activity is more sensible to the postmortem delay effect.