Purpose To employ PK modeling and clinical trial simulations for the selection of an appropriate dosing regimen for a Phase I/II clinical study to assess the therapeutic potential of an anti-IL-6 mAb in patients with metastatic renal cell carcinoma (RCC) following single ascending IV infusions. Methods: PK modeling and trial simulations were conducted using WinNonlin and Trial Simulator software. The model was developed using published data from patients with advanced multiple myeloma (van Zaanen, 1996). Results: Since IL-6 is a critical mediator in the pathophysiology of RCC, the dosing regimen for this study was selected based on neutralizing the blood level and endogenous production of IL-6. A minimum of a 300-fold molar excess of mAb to IL-6 was determined to be needed to fully block IL-6 bioactivity and inhibit tumor growth. This equates to a trough mAb concentration of 5 μg/mL. PK modeling and simulations predicted that doses of 1, 3, and 6 mg/kg administered on weeks 0, 3, 6, and 9 would result in mean serum antibody concentration exceeding the target trough concentration of 5 μg/mL for approximately 29, 33, and 35 weeks after the first infusion, respectively. Conclusions: PK modeling and simulations of published data from previous human experience should provide a sound rationale for selecting the appropriate dosing regimen for assessing the therapeutic potential of this study agent, in patients with renal cell carcinoma. Clinical Pharmacology & Therapeutics (2004) 75, P84–P84; doi: 10.1016/j.clpt.2003.11.323