Abstract The effect of the biguanides metformin and phenformin on glucose utilization in isolated cells was studied with IM-9 human lymphocytes. Both agents stimulated glucose consumption from the incubation media. Detectable effects of metformin were seen at 33 μmol/L and detectable effects of phenformin were seen at 1.7 μmol/L. Both agents, at similar concentrations, also stimulated [ 3H] 2-deoxy- d-glucose uptake. Studies with phenformin indicated that biguanides increase the V max of uptake without changing the Km. In contrast to the biguanides, IM-9 cells insulin did not influence either glucose consumption or [ 3H] 2-deoxy- d-glucose uptake. These data provide evidence, therefore, that biguanides may directly influence the cellular utilization of glucose.