trans-Monounsaturated acids account for up to 3% of the total octadecenoic acyl chains of human brain lipids. To investigate the influence of trans-acids on desaturation and chain elongation of fatty acids, in vitro and in vivo experiments with rat brain were performed. In the in vitro assays of delta 9 desaturation, delta 6 desaturation and chain elongation, trans,trans-dienoic acid was inhibitory, particularly to chain elongation. Slight differences between the inhibitory effects of trans-monoenoic acids and their cis-isomers were observed. In an in vivo model, unlabeled fatty acid (stearate, oleate, elaidate, linoleate, linoelaidate, arachidonate, or trans-monoene from margarine) was injected simultaneously with [1-14C] linoleic acid into the brains of suckling rats. Linoelaidate and oleate inhibited desaturation and elongation of linoleate, whereas elaidate, stearate and trans-monoene from margarine were stimulatory. While the demonstration of differences between cis and trans monenic isomers required relatively high levels of the test acids, it appears that trans-acids can influence desaturation and elongation enzymes that lead to acyl chain modification in the central nervous system.