Human sarcoma-bearing limb substrate utilization was characterized by studying 10 otherwise healthy patients with extremity sarcomas (five osteosarcomas, five soft tissue sarcomas). All patients were studied in the postabsorptive state. Extremity blood flow was measured using a non-invasive capacitance plethysmograph. Percutaneous arterial and venous effluent blood samples from the tumor-bearing (TB) and control extremity were obtained and flux was calculated for free fatty acids (FFA), glucose, and amino acids. The control limb showed a release of amino acids similar to that reported previously. There was a dramatic difference in the TB extremity, which consistently released fewer amino acids. Both the TB and control limbs released FFA at the same rate. A significant difference in glucose uptake between TB and control limbs was noted for soft tissue sarcoma patients but not osteogenic sarcoma patients. The amount extracted correlated with excised tumor size and gluconeogenic amino acid release from the contralateral normal limb. This study suggests that the tumor-bearing limb ignores the inherent conservation mechanisms in the postabsorptive state and continues to utilize substrate, apparently at the expense of host tissues.