The human colon carcinoma cell line, HCT 116, can be grown in chemically defined media in the absence of exogenous growth factors. The addition of transferrin and insulin will significantly stimulate growth. The interaction of these growth factors with their receptors was studied to determine whether the synergistic action of insulin and transferrin on growth involved alterations in the growth-factor receptors. Redistribution of the transferrin receptor occurred in the presence of transferrin or transferrin plus insulin. The presence of insulin in the growth media resulted in occupation of cell-surface insulin receptors without a reduction in total insulin binding. Addition of transferrin with insulin resulted in a decrease in insulin binding to its receptor, with no alteration in receptor affinity. It appears that transferrin plays a role in regulating the insulin receptor and that this may contribute to the synergistic effect of insulin and transferrin on growth.