Here we report a patient with molecularly defined severe congenital PAP due to a previously undescribed autosomal recessive mutation in the alpha chain of the GM-CSF receptor. This mutation leads to a stop of transcription and to a lack of functional protein. The GM-CSF induced responses are mediated through activation of the transcription factor PU.1 and include increased surfactant catabolism and CD11b expression [20] . Impairment of the latter was shown directly in mononuclear cells of the patient after stimulation with GM-CSF. Impaired GMCSF receptor activation of alveolar macrophages leads to decreased surfactant catabolism and accumulation of surfactant in the alveolar space, i.e. alveolar proteinosis.