During activation the lymphocyte attains functional insulin receptors with precise regulation, a consequence of insulin concentration manipulations. These studies test the hypothesis that insulin receptor (+) monocytes monitor insulin concentrations, so instructing the T lymphocytes. Monocyte-enriched populations were incubated with insulin (0-10(-6) M) followed by co-culture with T lymphocytes and an activating stimulus. A dose-related fall in T lymphocyte insulin receptor binding was observed that was specific for the monocyte as the signalling cell and for insulin as the signal received. Monocytes from normal volunteers during a euglycemic, hyperinsulinemic clamp were cultured with T lymphocytes and an activating stimulus. A decline in specific insulin receptor binding on T lymphocytes was observed, which Scatchard analysis demonstrated to be a consequence of reduction in receptor numbers. These studies demonstrate that the receptor (+) monocyte perceives the concentration of insulin and passes this information to T lymphocytes regulating the number of activation-induced insulin receptors. The interplay between the monocyte and T lymphocyte parallels the interaction of these cell types for recognition of antigen.