To study the effect of interleukin-6 (IL-6) on glucose transport, 2-deoxy-D-glucose (2-DOG) uptake in 3T3-L1 adipocytes after incubation with IL-6 was measured. IL-6 increased 2-DOG uptake maximally after 5 hours by 30 +/- 12%, with a half-maximal effect at an IL-6 concentration of approximately 800 U/mL. 3-O-methylglucose uptake was stimulated in a similar way, indicating that IL-6 enhanced glucose transport rather than phosphorylation. IL-6-induced glucose transport was additive to the effect of insulin. Addition of cycloheximide did not affect the stimulatory action of IL-6, although cycloheximide itself had profound effects on basal glucose transport. We conclude that IL-6 may enhance glucose uptake by increasing GLUT-1 intrinsic activity.