Studies were carried out to relate the changes of the fatty acid and lipid composition of rat microsomes with the modification of the activity of the linoleic acid desaturation evoked by an essential fatty acid deficient diet. Two steps were shown in the progression of the essential fatty acid deficienty. In a first step shown at three days of essential fatty acid deficiency the fatty acid composition was changed by decreasing linoleic and arachidonic acids and increasing oleic and eicosatrienoic (-9) acids. No change was found in the lipid distribution and approximate V and Km of the linoleic acid desaturation. In this first step the unsaturated/saturated fatty acids ratio fell in spite of the synthesis of eicosatrienoic (n-9) acid that was produced without any change of enzyme activity. In a second step shown at 15 days of essential fatty acid deficiency the change of the fatty acid composition was greater but the unsaturated/saturated acid ratio was restored. An increase of triacylglycerols and a decrease of phospholipids was also detected together with an enhanced activity of linoleic acid desaturation (higher approximate V) and a higher approximate Km. The increase of the V of linoleic acid desaturation is considered to be evoked by an increased level of active delta-6 desaturase. The increased activity of the delta-6 desaturase in this second period is a secondary and important response of the cell to maintain the unsaturated : saturated acid ratio and fluidity of the membrane.