This study aims to investigate quantitatively the direct correlation between the mechanical strength of powder agglomerates and their dispersion into aerosols by a dry powder inhaler. Agglomerates of mannitol as a model drug-only formulation were prepared by a rolling method followed by exposure to various relative humidity (RH: 55%, 82%, 86% and 90%). The agglomerate strength was obtained from the compression of single agglomerates at a selected speed rate using an Instron testing machine. The dispersion performance (FPF(Loaded)) was determined at flow rates of 60 and 1001 min(-1) using an Aeroliser (R)} coupled to a multistage liquid impinger. Results showed an inverse linear relationship between the agglomerate strength and the dispersion performance. An increase in strength from 3 to 183 kPa resulted in a significant drop (P < 0.05) of 18% in the FPF(Loaded). Agglomerates containing 'solid bridges' exhibited higher strength (three to eight times) and lower FPF (5-15%, corresponding to 86% and 90% RH) compared to those containing 'liquid bridges'. These results have provided direct information on the agglomerate strength and its quantitative relationship with powder aerosol performance. (C) 2011 Elsevier Ltd. All rights reserved.