The purpose of the present work was to analyze the moisture sorption and distribution of pharmaceutical powders at various relative humidities (RHs), to investigate its impact on the inter-particle adhesion force as well as the performance of drug delivery through a dry powder inhaler (DPI). Moisture sorption isotherms were measured and the moisture distribution was analyzed using the GAB method and the Young-Nelson equations for Inhalac 230 (R), salbutamol sulfate, and the binary mixture. Adhesion force of the mixture decreased with RH initially, and then increased upon further increase in RH. An increase in the fine particle fraction of emitted dose (FPF(em)) with RH at low moisture contents appeared to be the result of a reduction in electrostatic force due to charge dissipation associated with moisture sorption, while a decrease in the FPFem at high moisture contents arose from the liquid bridge force. It appeared that the emission efficiency was significantly affected by the electrostatic force. The results suggested that electrostatic force not only influenced the drug FPFem but the drug emission efficiency as well, while the liquid bridge force mainly affected the aerosol FPFem for the DPI system investigated. The results indicated that the influence of the RH on the performance of DPI drug delivery was through its impact on the fundamental electrostatic and liquid bridge forces depending on the distribution of the adsorbed moisture content. (c) 2008 Elsevier Ltd. All rights reserved.