PURPOSE: To characterize the effects of NaCl concentration on tissue electrical conductivity, radio-frequency (RF) deposition, and heating in phantoms and optimize adjunctive NaCl solution injection for RF ablation in an in vivo model. MATERIALS AND METHODS: RF was applied for 12-15 minutes with internally cooled electrodes. For phantom experiments (n = 51), the NaCl concentration in standardized 5% agar was varied (0%-25.0%). A nonlinear simplex optimization strategy was then used in normal porcine liver (n = 44) to determine optimal pre-RF NaCl solution injection parameters (concentration, 0%-38.5%; volume, 0-25 mi). NaCl concentration and tissue conductivity were correlated with RF energy deposition, tissue heating, and induced coagulation. RESULTS: NaCl concentration had significant but nonlinear effects on electrical conductivity, RF deposition, and heating of agar phantoms (P < .01). Progressively greater heating was observed to 5.0% NaCl, with reduced temperatures at higher concentrations. For in vivo liver, NaCl solution volume and concentration significantly influenced both tissue heating and coagulation (P < .001). Maximum heating 20 mm from the electrode (102.9 degreesC +/- 4.3 [SD]) and coagulation (7.1 cm +/- 1.1) occurred with injection of 6 mL of 38.5% (saturated) NaCl solution. CONCLUSION: Injection of NaCl solution before RF ablation can increase energy deposition, tissue heating, and induced coagulation, which will likely benefit clinical RF ablation. In normal well-perfused liver, maximum coagulation (7.0 cm) occurs with injection of small volumes of saturated NaCl solution.