Dietary nucleotides have been described to play multiple physiological roles. We examined the effect of feeding, for 4 weeks, nucleotide-supplemented diets (N-50 and N-250) on red blood cell (RBC) membrane fatty acid composition in weanling rats. Long-chain polyunsaturated fatty acids (LC-PUFA) of the n-6 series, especially arachidonic acid, increased in total RBC phospholipids in N-50 and N-250 groups. Concentrations of LC-PUFA of the n-3 series were preserved or slightly decreased. Saturates and monoenates also decreased. Phosphatidylethanolamine and sphingomyelin followed the variations observed for total phospholipids. Phosphatidylcholine showed a different response; saturated fatty acids increased while n-6 LC-PUFA decreased. Dietary nucleotides seem to affect the conversion of essential fatty acids to their long-chain derivatives in weanling rats in a similar way to that occurring in newborn infants during early life. These results show that the rat may be a valid model with which to study the biochemical mechanisms by which dietary nucleotides affect fatty acid desaturation.