Two human neuroblastoma cell lines, NCG and GOTO, were used to study the cytotoxic effect of gamma linolenic acid (GLA). The cell growth inhibition of these culture cells by GLA was found to be associated with striking membrane fatty acid modification. When culture cells were exposed to 20 micrograms/ml and 60 micrograms/ml GLA for 48 hr, polyenoic acids in cell membrane phospholipids (PC, PE, PI, PS) and triglyceride significantly increased; 1.8-21.0 fold for NCG and 1.04-11.5 fold for GOTO, in association with decreased monoenoic acids. The most remarkable changes were; increase of C18:3, C20:3, C20:4 and decrease of C18:1. CoQ10 (50 micrograms/ml) and vitamin E (10 microM) shown to protect against the cytotoxic effect of GLA did not modify the incorporation of GLA into tumor cells. These results indicate that the antitumor effect of GLA is probably due to cellular dysfunction caused by fatty acid modification after GLA incorporation.