The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are bioactive lipids derived from the n-6 family of polyunsaturated fatty acids that are essential fatty acids. Symptoms of essential fatty acid deficiency in rats - growth retardation, scaly skin, and increased transepidermal water loss - can mainly be attributed to lack of linoleic acid as a structural element of the epidermis. Arachidonic acid, however, also serve essential functions, particularly in cellular signalling via its precursor role for numerous oxygenated derivatives such as prostaglandins, leukotrienes, hepoxilins and other eicosanoids. Furthermore, arachidonic acid is also a structural part of endocannabinoids that have signalling functions in relation to modulation of neurotransmitter release, which might involve physiological and pathophysiological phenomena such as regulation of appetite, energy metabolism, pain perception, memory and learning. Furthermore, along with AEA formation other acylethanolamides are always formed - e.g., oleoylethanolamide (OEA), that can inhibit food intake, and palmitoylethanolamide, that is anti-inflammatory - possibly through activation of peroxisome proliferator activated receptor alpha (PPAR alpha) and/or GPR119. As all these unsaturated fatty acids are ingested daily in smaller or larger amounts, one can ask whether different dietary fats can affect the levels of these fatty acids in the tissues and thereby the quantitative formation of these bioactive signalling molecules. Generally, in vivo arachidonic-acid-derived eicosanoid production can be increased and decreased by prolonged feeding with pharmacological levels of arachidonic acid and long-chain (n-3) fatty acids (fish oil), respectively. Changes in levels of these two fatty acids within the traditional human diet hardly affects the eicosanoid production, however. Moreover, preliminary data suggest that dietary intake of arachidonic acid and fish oil also doesn't easily affect endocannabinoid formation; however, dietary fat in terms of saturated, polyunsaturated and monounsaturated seems to affect tissue levels of AEA, 2-AG and OEA.