We have previously shown that asparagine alone induces a 10-15-fold increase in ornithine decarboxylase (ODC) mRNA level in DF-40 mouse neuroblastoma cells. The induction is due to an accumulation of ODC mRNA through a post-transcriptional stabilization mechanism (Chen, Z.P. and Chen, K.Y. (1992) J. Biol. Chem., 267, 6946-6951). In the present study we showed that asparagine induced ODC gene expression in v-Ha-ras-transformed 3T3 (ras-3T3) cells but not in 3T3 cells. Other growth related genes including c-src, c-ras, and c-fos were not affected by asparagine in ras-3T3 cells. Southern blot analysis indicated that the pronounced asparagine effect was not due to ODC gene amplification in ras-3T3 cells. The effect of asparagine on the induction of ODC mRNA could account for the significant increases in the ODC activity in ras-3T3 cells. We also examined the effect of asparagine on ODC gene expression in human KD cells and their transformed counterparts. Our findings strongly suggest that the induction of ODC mRNA by asparagine may represent a component of an altered growth regulatory program associated most prominently with cell transformation.