12-O-Tetradecanoylphorbol-13-acetate (TPA), a highly active tumor-promoting agent, rapidly accelerates deoxyglucose transport in bovine lymphocytes. This acceleration in rate is dose-dependent and proceeds without evidence of a lag period to achieve a maximal response within 10 min. Structure-activity studies showed that the activity of various phorbol derivatives for the stimulation of glucose transport closely parallels their potency as comitogens and stimulators of phosphatidyl choline synthesis in bovine lymphocytes and as tumor promoters on carcinogen-initiated mouse skin. The acceleration of glucose transport by TPA proceeds in the absence of oxygen and in the presence of retinoic acid and 5,8,11,14-eicosatetraynoic acid (ETYA). This situation is in contrast to the TPA stimulation of choline phospholipid synthesis and amino acid transport which exhibits a lag and a sensitivity to anaerobiosis, retinoic acid, and ETYA. These results suggest that the stimulation of glucose transport by TPA is an oxygen-independent early event resulting from a direct action of the tumor promoter on the cell membrane of the lymphocyte; this action of TPA appears antecedent to the oxygen-dependent/retinoid-sensitive events.