Insulin resistance is probably the defining feature of the metabolic syndrome and is an important determinant of plasma triglyceride (TG) concentrations. We sought to investigate whether insulin resistance influenced the metabolism of VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). Sixteen (eight men, eight women) middle-aged, normoglycaemic subjects participated. VLDL 1 and VLDL 2 apolipoprotein (apo) B metabolism was followed using a deuterated leucine tracer and insulin resistance was estimated using homeostasis model assessment (HOMA). HOMA-estimated insulin resistance (HOMA I R ) significantly and strongly correlated with the VLDL 1 production rate (r = 0.69, P < 0.01) and VLDL 1 apo B pool size (r = 0.59, P = 0.02), but these relationships were not evident for VLDL 2 . Conversely, HOMA I R was not significantly related to the fractional rate of transfer of VLDL 1 to VLDL 2 but was significantly related to the fractional rate of transfer from VLDL 2 to IDL (r = 0.61, P = 0.01). HOMA I R was not significantly related to the fractional rate of direct catabolism for either VLDL 1 or VLDL 2 . These results suggest a role for insulin resistance in the determination of hepatic VLDL 1 production and highlight the independent regulation of VLDL 1 and VLDL 2 metabolism.