We aimed to evaluate the feasibility and tolerability of the newly developed thermotherapy using magnetic nanoparticles on recurrent glioblastoma multiforme. Fourteen patients received 3-dimensional image guided intratumoral injection of aminosilane coated iron oxide nanoparticles. The patients were then exposed to an alternating magnetic field to induce particle heating. The amount of fluid and the spatial distribution of the depots were planned in advance by means of a specially developed treatment planning software following magnetic resonance imaging (MRI). The actually achieved magnetic fluid distribution was measured by computed tomography (CT), which after matching to pre-operative MRI data enables the calculation of the expected heat distribution within the tumor in dependence of the magnetic field strength. Patients received 4-10 (median: 6) thermotherapy treatments following instillation of 0.1-0.7 ml (median: 0.2) of magnetic fluid per ml tumor volume and single fractions (2 Gy) of a radiotherapy series of 16-70 Gy (median: 30). Thermotherapy using magnetic nanoparticles was tolerated well by all patients with minor or no side effects. Median maximum intratumoral temperatures of 44.6 degrees C (42.4-49.5 degrees C) were measured and signs of local tumor control were observed. In conclusion, deep cranial thermotherapy using magnetic nanoparticles can be safely applied on glioblastoma multiforme patients.