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In-vivo porcine studies on the effect of nanosecond high-voltage pulses on liver tissue have shown that cell death can be induced in well-defined tissue volumes without damaging collagen-predominant structures. Comparison of the experimental results with the results of a 3-D finite element model allowed us to determine the threshold electric field for cell death. For 30, 100-ns-long pulses this was found to be in the range from 12 to 15 kV/cm. Modeling of the temperature distribution in the tissue using Pennes' bioheat equation showed that the lethal effect of nanosecond pulses on cells is nonthermal. Muscle contractions, generally caused by high-voltage pulses, were significantly reduced for the 100-ns pulses compared to microsecond-long pulses. The results of these studies indicate that high-voltage nanosecond pulses reliably kill normal liver cells in vivo, and therefore, may be useful for liver tumor treatments.