Laser-induced thermotherapy is an in situ ablation method for the local treatment of liver tumors. The basic prerequisite for induction of adequate treatment volumes for clinical use was the development of a thermostable application system. In an ex vivo test series, the specially developed application system (diffuser tip) with 5760 J had a higher thermic loading capacity than the Ringmode applicator with 4200 J, thus enabling the induction of significantly larger lesions with a volume of 7.6 cm3. The results of a further in vivo test series demonstrated that the lesions were subject to a four-phase connective-tissue organization within a 6-month period. Furthermore, the same laser energy (4200 J) was associated with a significantly lower lesion volume of 2.5 cm3 in the in vivo than in the ex vivo test series. The influence of liver perfusion on the inducible lesion volume was examined in a further animal experimental study. By temporarily interrupting hepatic blood perfusion (Pringle's maneuver) during laser application, the effective volume could be increased to 50.3 cm3 (P < 0.01) using an optical beam splitter. These results show that the technical prerequisites for reliable clinical application of laser-induced thermotherapy have been fulfilled.