We studied the metabolism of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) particles that did or did not have apolipoprotein E (apoE) in 12 normolipidemic women by endogenously labeling plasma apolipoprotein B. The plasma was separated into bound (E+) and unbound (E−) fractions by use of a monoclonal antibody (1D7), and the fractions were ultracentrifuged to yield E+ and E− subfractions of light and dense VLDL and IDL. VLDL E+ and IDL E+ were produced mainly by the liver. VLDL E+ and IDL E+ had lower fractional catabolic rates and much higher apolipoprotein C-III (apoC-III) content than did the corresponding E− particles. Most light VLDL apoE+ underwent lipolysis to dense VLDL E+ with reduced apoC-III content, which was removed from the circulation without conversion to IDL. In contrast, most light VLDL apoE−, poor in apoC-III, was removed from the circulation, and a smaller proportion underwent lipolysis to dense VLDL E−. Most dense VLDL E− underwent lipolysis to IDL E−. The rate constant for lipolysis of dense VLDL to IDL was greater for E− than for E+, and the rate constant for clearance from plasma was greater for dense VLDL E+ than for E−. In conclusion, metabolism of human VLDL particles is influenced by their content of apoE, further modulated by the coexistence of apoC-III.