Perceptions that rural populations are inevitably healthier and live longer than urban populations are increasingly being challenged. But very few publications have investigated the extent to which these putative differences can be explained by variation in area composition. Existing publications have tended to use conventional deprivation measures, often thought to mask rural deprivation by favourable averages. Further, they have typically been based on large and variably-sized geographical units, or confined to studies of a single region or cause of death. This study examines differences in mortality between rural and urban areas in the entire population of England and Wales for 2002e2004. It uses the most up-to-date small geographical units of similar size and homogeneity of population together with the recently-introduced Rural and Urban Area Classification, and adjusts for five different deprivation measures (including modern composite indices). The causes of death investigated were all-cause mortality, cancer, lung cancer, respiratory disease, circulatory disease, suicide and accidents. Particular points of focus for the study were the potential for interaction between deprivation and rurality, and the importance of choice of deprivation measure in quantifying the relationships between mortality, rurality and deprivation. Choice of deprivation measure was not found to alter the substantive conclusions of any analysis, and little evidence for differential effects of deprivation in rural and urban areas was uncovered. Differences between rural and urban areas in all-cause, circulatory disease and cancer mortality could largely be accounted for by adjusting for deprivation. For these causes of death, therefore, rural populations were not found to be inherently healthier than their urban counterparts. However, substantial residual differences between rural and urban areas were found in comparisons of mortality from lung cancer and respiratory disease, mortality being lower in rural areas. Stronger relationships between rurality and mortality were found in ‘village and dispersed’ settlements.