In the Mediterranean area, which is climatically stressed by limited water resources and extremes of heat, climate variations are known to play a crucial role in the ecosystems and environment. Investigating how climate has changed in the past may help us to understand how it may change in the future and its consequences on temperature and water resources. The Gran Dolina sequence (north-central Spain) provides a unique long paleontological and archaeological record spanning the Mid-Brunhes (ca. 450 ka) climatic transition. A fossil amphibian- and squamate-based reconstruction of temperature and precipitation shows marked peaks that have been related to various interglacial peaks in accordance with numeric dates and paleomagnetic and biochronological data. An analysis of climate and herpetofaunal assemblage changes during the interglacial periods reveals that (1) post-Mid-Brunhes Event (MBE) interglacials were warmer than pre-MBE interglacials, (2) pre-MBE interglacials were warmer than present day, and (3) there were lower levels of rainfall in post-MBE interglacials than in pre-MBE interglacials. The climate trend in the Mediterranean area was found to be congruous with global climate changes as reconstructed from ice and sea-surface temperature records over the past million years.