Competition between the (n - 3) and (n - 6) types of highly unsaturated fatty acids can diminish the abundance of (n - 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by (n - 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18:2 (n - 6) and 18:3 (n - 3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505-516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of (n - 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic or other disorders that are mediated by (n - 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated (n - 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon (n - 3) fatty acids compared to that for the 18-carbon (n - 3) fatty acid in decreasing the ability of dietary 18:2 (n - 6) to maintain 20:4 (n - 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n - 3 fatty acids in the elongation/desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n - 6 vs. the n - 3 type indicated a greater competitive effectiveness of 20:4 (n - 6) relative to 20:5 (n - 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the (n - 3) and (n - 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids.