delta 6- and delta 5-Desaturation of essential fatty acids of n-6 and n-3 series are required for the biosynthesis of polyunsaturated fatty acids (PUFAs), which are precursors of eicosanoids and constituents of membrane phospholipids. This pathway could be of special importance during the perinatal period, when PUFAs accretion in the central nervous system is very active. However, experimental evidence of delta 6- and delta 5-desaturase activities in man is very scarce, and no data are available for newborns. We report the delta 6- and delta 5-desaturase activities detected in human liver microsomes from three neonates who died from associated malformations. Radiochemical assays of delta 6- and delta 5-desaturase activities performed with reverse phase HPLC analysis of the products in the n-6 series ranged from 4.8-13.6 to 3.2-16.4 pmol substrate converted.min-1.mg-1 microsomal proteins, respectively. In the n-3 series delta 6-desaturase activity ranged from 5.3 to 12.8 pmol.min-1.mg-1. The relationships between enzyme activities and substrate concentrations suggest excess substrate inhibition for n-6 and not for n-3 fatty acids. These results demonstrate significant delta 6- and delta 5-desaturase activities in human liver of neonates, but this activity was lower than previously reported in adult humans and in mammals, especially rodents.