BACKGROUND Previous studies have analyzed the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHO-DAS II) using classical omnibus measures of scale quality. These analyses are sample dependent and do not model item responses as a function of the underlying trait level. The main objective of this study was to examine the effectiveness of the WHO-DAS II items and their options in discriminating between changes in the underlying disability level by means of item response analyses. We also explored differential item functioning (DIF) in men and women. METHODS The participants were 3615 adult general practice patients from 17 regions of Spain, with a first diagnosed major depressive episode. The 12-item WHO-DAS II was administered by the general practitioners during the consultation. We used a non-parametric item response method (Kernel-Smoothing) implemented with the TestGraf software to examine the effectiveness of each item (item characteristic curves) and their options (option characteristic curves) in discriminating between changes in the underliying disability level. We examined composite DIF to know whether women had a higher probability than men of endorsing each item. RESULTS Item response analyses indicated that the twelve items forming the WHO-DAS II perform very well. All items were determined to provide good discrimination across varying standardized levels of the trait. The items also had option characteristic curves that showed good discrimination, given that each increasing option became more likely than the previous as a function of increasing trait level. No gender-related DIF was found on any of the items. CONCLUSIONS All WHO-DAS II items were very good at assessing overall disability. Our results supported the appropriateness of the weights assigned to response option categories and showed an absence of gender differences in item functioning.