The IL-13Ralpha2 gene encodes for a 65 kDa protein that forms one of the subunits of the interleukin-13 (IL-13) receptor. This gene is highly expressed in various types of human tumors including malignant gliomas. The expression level of IL-13Ralpha2 was examined in a total of 45 tissue samples of anaplastic astrocytomas (AAs) World Health Organization (WHO) grade III, glioblastomas (GBMs) WHO grade IV, and first-recurrent glioblastomas (frGBMs) after treatment with radiation and chemotherapy. IL-13Ralpha2 expression was detected by semiquantitative reverse transcription real-time polymerase chain reaction (PCR) using ABI PRISM 7700 and Qiagen QuantiTect SYBR Green PCR kits. The expression level of IL-13Ralpha2 (15 fold) was significantly reduced in frGBMs compared to the primary GBMs (p = 0.014), and significantly reduced by more than 15 fold (p = 0.003) in all untreated malignant astrocytomas (AAs and GBMs) compared with treated frGBMs. Expression of IL-13Ralpha2 seems to be lower in frGBMs compared to GBMs. The promising antitumor effect of IL-13 cytotoxin could be greatly reduced in frGBM or only achievable with higher amounts of cytotoxin, due to the significantly lower expression of the cytotoxin's target structure.