The heat, air and moisture transfer through external walls in general and lightweight concrete hollow blocks in particular has a direct influence on energy consumption in buildings and hygrothermal performance of indoor environment. The aim of this paper is to present the hygrothermal performance of a space enclosed with pumice aggregate concrete blocks (PACB) located in the environmental conditions of Istanbul, simulated by EnergyPlus, and to discuss the effect of orientation and thermal insulation material on hygrothermal behaviour of spaces and wall assemblies. Hygrothermal performance within south and north oriented zones and having different wall assemblies are assessed with the related parameters such as mean radiant temperature and relative humidity. Temperature distribution results within the assemblies are then comparatively discussed. In accordance with the hygrothermal simulation results it can be said that the change of orientation and alternative layers of the wall affects the hygrothermal performance of external walls and the risk of moisture accumulation through it.