Malignant pleural mesothelioma (MPM) is a highly chemoresistant cancer with a poor prognosis. Hypoxia is a specific property of solid tumours, contributes to low apoptotic potential, and can be selectively targeted by bioreductive drugs. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a subunit of a heterodimeric transcription complex that regulates several genes associated with tumour progression and anti-apoptosis. In this study, we measured for the first time the expression of HIF-1alpha in MPM. Our results show that HIF-1alpha is commonly expressed in MPM but not in normal mesothelium, consistent with the presence of hypoxia. HIF-1alpha does not appear to predict survival; however, this study suggests that bioreductive drugs should be investigated in clinical trials of MPM.