The paper proposes a new approach to the estimation of casualties in buildings damaged in earthquakes, based on an understanding of the volume loss within the building and the spread of debris beyond the envelope of the building. The study starts by developing a set of estimated relationships between lethality rates and volume loss for different common building types, derived from expert judgement based on reported casualty rates worldwide, and on experience of the causative collapse mechanisms, and the associated volume loss. Three datasets have then been compiled based on worldwide earthquakes. Firstly, a dataset of the causes of death and injury for more than 8300 earthquake victims has been assembled. The dataset records, for each affected individual, the type, level and location of injury, the type of building and its damage state. Secondly, using an earthquake damage photographic database, a subset of more than 450 heavily damaged buildings has been selected and these have been analysed to estimate the volume loss, and to associate volume loss for buildings with very heavy damage and collapse with different construction types and collapse mechanisms. Lastly, to assess potential casualties from external falling hazards (chimneys, parapets etc.), a further study of 361 severely damaged buildings recorded in the photographic database was carried out, to identify the extent and type of external debris generated, and its relationship to building type, damage state and damage mechanism. In conclusion, the paper discusses how volume loss and debris characteristics could be estimated as a standard component of fragility estimation in order to improve reliability of human casualty estimation in earthquake loss models.