This thesis investigates an aspect of Southampton's history not previously explored, the effects of smallpox on the town and its environs during the eighteenth century. The work provides a new viewpoint on the town's efforts to establish and maintain itself as a sea bathing and spa health resort, while at the same time supporting sick and wounded military personnel, prisoners of war and billeted troops. The study undertakes a detailed analysis of the town's inoculation records, held within the `Inoculation Book' and from this produces new information on the prevailing attitudes towards the poor, smallpox and inoculation in the town. Brief comparisons with Salisbury and Winchester demonstrate two alternative attitudes towards outbreaks of the disease and the use of inoculation, within these communities. The thesis attempts to assess the efficacy of each approach. This would merit further detailed investigation in the future. Throughout the eighteenth century there were reports of inhabitants fleeing from the towns to rural areas during smallpox outbreaks. The thesis investigates the plausibility of this premise for the Southampton area, and drawing on modem scientific research together with established ecological observation, places these combined findings within the historical context. This has resulted in an entirely new and important evaluation of the role of the rural ecological environment in the survival of earlier generations and would benefit from further investigation in other areas of the country.