The plant lectin (wheat germ agglutinin, WGA) produces several alterations in the ability of fat cells to bind and respond to insulin. Although WGA markedly stimulated glucose oxidation, it caused only a modest stimulation of glucose transport. WGA (0.25-20 micrograms/ml) increased the binding of insulin by adipocytes, apparently by increasing the binding affinity of the insulin receptor. With low WGA concentrations (0.25-2.5 micrograms/ml), the elevation in binding was accompanied by an increase in the sensitivity of the adipocytes to insulin stimulation of glucose transport. However, the sensitivity of these cells to vitamin K5 and H2O2 was not altered. With higher WGA concentrations (5-20 micrograms/ml), stimulation of the glucose transport system by insulin, vitamin K5, or H2O2 was markedly inhibited, an effect that is reversed by the addition of ovomucoid. These findings suggest that low WGA concentrations increase the affinity of the insulin receptor and the insulin sensitivity of the cells. At higher concentrations, the lectin appears to act at another site(s) to inhibit the activation of the transport system by insulin or other agents.