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Insulin-like growth factor-I circulates in serum either in free form or bound to insulin-like growth factor-binding proteins that modulate its bioavailability. Insulin-like growth factor-binding proteins interfere with insulin-like growth factor-I assay, which remains technically difficult. Many assays have been developed, but their results are somewhat discordant. The choice of separation method, standard and tracer considerably influences the results. The circulating concentration of insulin-like growth factor-I, however, is clearly dependent on nutritional status, and total levels are a valuable marker of nutritional status. The clinical utility of free insulin-like growth factor-I assay and simultaneous assay, in the same sample, of total insulin-like growth factor-I and its binding proteins (reflecting the bioavailable insulin-like growth factor-I fraction), remains to be evaluated.