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It has been proposed that hyperinsulinaemia may cause or exacerbate insulin resistance. The present studies were undertaken to test this hypothesis in man. Glucose utilization, glucose production, and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations (∼80 and ∼1700 mU/l), and monocyte and adipocyte insulin binding were measured in normal volunteers on two occasions: once after 40 h of hyperinsulinaemia (25–35 mU/l) produced by infusion of insulin and once after infusion of saline (75 mmol/l; plasma insulin ∼10 mU/l). After 40 h of hyperinsulinaemia, glucose utilization and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations were both slightly, but significantly, reduced compared with values observed after the infusion of saline (p<0.05), whereas glucose production rates were unaffected. Monocyte …