In a companion study (Verbanck S, Schuermans D, Vincken W, and Paiva M, J Appl Physiol 90: 1754-1762, 2001), we investigated whether saline aerosol bolus tests could also be used to detect proximal, as opposed to peripheral, airway alterations. We studied 10 never-smokers before and after histamine challenge, obtaining, for various volumetric lung depths (VLD), saline bolus-derived indexes computed by discarding aerosol concentrations below either 50% of the exhaled bolus maximum (half-width, H) or below cutoffs ranging from 5 to 25% (standard deviation, sigma(5%)-sigma(25%)) and skew (sk(5)-sk(25%)). Multiple-breath N(2) washout-derived indexes of conductive (S(cond)) and acinar (S(acin)) ventilation inhomogeneity were also determined. After histamine, S(cond) significantly increased (P = 0.008) whereas S(acin) remained unaffected, indicating purely conductive airway alteration. Consistent with this observation, sk(5%) (or sk(25%)) was increased to the same extent at all VLD, and sigma(5%) was increased preferentially at low VLD. By contrast, H and sigma(25%) displayed preferential increases at high VLD, a pattern similar to that induced by peripheral alterations. The present work shows that proximal airway alteration can be reliably identified by saline bolus tests only if these include measurements at low and high VLD and if bolus dispersion is quantified as a standard deviation with a low cutoff.