U-937 monocytes, a human cell line, respond acutely to insulin by internalization of the insulin receptor and acceleration of fluid-phase pinocytosis. In the present studies, both processes were shown to require energy and both were dependent on the number of insulin receptors. Monocytes with a reduced number of insulin receptors, ie, down-regulated by a 16-hour insulin treatment, had a markedly reduced response to insulin-stimulation of pinocytosis and a decrease in the amount of insulin receptors internalized. This latter feature resulted, however, from the reduction in the cellular content of insulin receptors. The proportion of receptor internalized during a 30-minute acute treatment with insulin (eg, 59% of the cell surface receptors) was slightly greater than the proportion internalized in control cells. Therefore, down-regulation does not selectively destroy receptors that cycle, leaving only a subpopulation of receptors anchored in the membrane. Apparently, there is only one population of insulin receptors, all of which are equally competent with respect to internalization. Although these results suggest a close relationship between pinocytosis and receptor internalization, it was possible to separate the two systems. The addition of poly- l-lysine produced a marked stimulation of fluid-phase pinocytosis in the absence of any increase in insulin receptor internalization. Thus, movement of the receptor into the internal pool requires more than an increase in the rate of pinocytosis. Rat adipocytes were also studied, and the results differed in several aspects from those of U-937 monocytes. Although insulin stimulated adipocyte receptor internalization, it did not increase fluid-phase pinocytosis. Also, energy depletion itself increased receptor internalization. Thus, even though both cell types undergo accelerated receptor cycling during acute insulin stimulation, the molecular events responsible for this phenomenon differ at some step in the overall process. These studies also show that an increased rate of pinocytosis is of itself not enough to cause an enhanced movement of the insulin receptor to internal pools.