The fatty acid amide family (FAEs), including arachidonoylethanolamide (anandamide, AEA), 2-arachidonoylethanolamide (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are a group of lipids which possess anti-inflammatory and anti-nociceptive properties. Many of the physiological responses to FAEs are thought to be due to their action at the cannabinoid receptors (CBs). Recent data suggest that FAEs can bind to and activate the PPAR (peroxisome-proliferator-activated receptor) family of nuclear receptor transcription factors in vitro and in vivo. Although the effects of FAEs on PPARs have been partly established, the mechanism by which FAEs are transported within the cells to their molecular targets at both the plasma membrane and within the nuclear remains unclear. Intracellular fatty acid binding proteins (FABPs) serve as intracellular acceptors of fatty acids; FABP3 and FABP7 are the major FABPs located in the brain, one of the major sites of synthesis and physiological action of FAEs. To assess the effects of FABP3 and FABP7 on PPAR-mediated transcriptional activation, CHO cells were transiently transfected with a luciferase reporter construct containing three PPRE (Peroxisome Proliferator Response Element) in combination with FABP3 or 7 and PPARα, β or γ. FABP3 was found selectively increase (2.2 folds, P < 0.001) PPARα-mediated transcriptional activation while FABP7 was found selectively increase (3.2 folds, P < 0.001) the transcriptional activation of PPARγ. No effects of FABP3 or 7 were observed upon the basal transcription activation of PPARβ. The FAEs, OEA and AEA, were shown to activate PPARα and PPARγ respectively. Treatment of cells transfected with PPARα and FABP3 with 10μM OEA caused a significant elevation of reporter gene over and above that obtained with either FABP3 or OEA alone. A similar result was obtained with PPARγ and FABP7 treated with 10μM AEA. The existence of FABP7 not only accelerated but also prolonged the effects of AEA on PPARγ in a time course assay while FABP3 didn't significantly change the time pattern of OEA's effects on PPARα. These studies suggest FABP3 and FABP7 may play important but diversified roles in intake, transport and degradation of FAEs in the brain. Further experiments are required to reveal the molecular basis and physiological relevance of the specificity of individual FABPs for different PPARs in the central nervous system.