Throughout much of the late eighteenth and early nineteenth centuries, the tropics and subtropics were constructed as a relatively homogenous realm. The supposed ‘pathological potency’ of these regions was assumed to render them particularly hazardous for European constitutions relative to ‘temperate’ locations. The interior of Africa represented one such apparently pestilential place. This paper examines how the experiences of nineteenth-century missionaries based at various stations in central southern Africa might have been influenced by popular and scientific debates focusing on environment, climate and health in Africa. We also illustrate how their perspectives may have challenged popular homogenized conceptualizations of interior Africa as a uniformly dangerous place for Europeans and helped to identify a spatially varied pathological geography of the region.