We have examined the ability of tumor necrosis factor-alpha (TNF) to stimulate hexose transport in 3T3-L1 fibroblasts. Activation of transport occurred in a dose- and time-dependent manner, with maximal stimulation (fourfold) occurring approximately 15 hours after exposure to 2.5 nM TNF. The protein synthesis inhibitor, cycloheximide, blunted TNF-induced 2-deoxyglucose uptake, suggesting that new synthesis was in part responsible for the observed increase. Increased hexose transport occurred concomitant with a 50% increase in general protein synthesis which preceded a fivefold stimulation of thymidine incorporation into DNA. Elevated hexose transport preceded an accumulation of glucose transporter (GLUT-1) mRNA. We have further demonstrated that the early accumulation of GLUT-1 mRNA is accompanied by accumulation of mRNA for both the prootooncogene c-fos as well as that for beta-actin. We suggest that these events represent the pleiotrophic growth factor-like properties of TNF-alpha.