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To assess whether urbanization influences the spatial ecology of a rare and protected venomous reptilian predator, the Gila monster Heloderma suspectum, we compared home range (HR) size and movement parameters at three sites varying in degree of urbanization in the Sonoran Desert. We predicted that the urban population of H. suspectum would exhibit smaller HRs, avoid human structures and show less movement. Multivariate analysis indicated that males generally exhibited larger HRs and had higher movement rates and activity levels than females at all three sites. Contrary to our predictions, however, HR size and movement parameters did not vary across the sites in relation to the level of urbanization. At the urban site, individuals often crossed narrow roads and regularly used artificial structures as refuges for extended periods. Furthermore, the population sex ratio at the urban site was female-biased, consistent with the expectation that occupation of larger HRs and higher movement rates results in higher mortality for males in urbanized areas. Gila monsters did not appear to alter certain aspects of their spatial ecology in response to low levels of human activity but additional work will be required to assess population viability and possible effects in the long term and with higher levels of urbanization.