Respiratory tract deposition data of ultrafine aerosol particles, hygroscopic particles and ambient particles in general are scarce. Measurements are associated with several difficulties. The objective of this work was to design a method for fast determination of highly size-resolved fine and ultrafine particle deposition, to be used on larger groups of human subjects in exposure studies and in typical ambient and indoor environments. The particle size distributions in dried samples of the inhaled and exhaled air are characterised with an electrical mobility spectrometer. A particle counter desmearing procedure reduces the spectrometer scan time. The precision and sensitivity of the method was tested for hygroscopic sodium chloride (NaCl) and hydrophobic Di-Ethyl-Hexyl-Sebacate (DEHS) aerosols in repeated identical experiments and experiments with different breathing frequencies on a single subject. The accuracy of the method was estimated by comparing results from three subjects with previous data obtained with monodisperse particles and with the well-established International Commission on Radiological Protection model (1994). Potential errors due to size shifts between the inhaled and exhaled samples and coagulation were simulated. The system has low losses in the studied particle size range (10–475 nm), typically 10% or less of the fraction deposited in the respiratory tract. Coagulation is noticeable at but can be corrected for up to . The precision in the determined deposited fraction is 0.02–0.08. The method is sensitive enough to quantify differences between breathing patterns and differences between hygroscopic and hydrophobic aerosols. Our results for NaCl and DEHS are in agreement with the ICRP 66 model [International Commission on Radiological Protection. (1994). Human respiratory tract model for radiological protection (ICRP Publication 66). Oxford, UK: Elsevier Science], and also suggest that the relative humidity in the respiratory tract is close to 99.5%. A respiratory tract deposition measurement can be done in 15–30 min. Recommendations are given for field applications of the method.