The receptors for IL-3, GM-CSF, and IL-5 share a common 5 subunit (5c), and mice have an additional IL-3 5 subunit (5~). We have independently generated mice carrying null mutations of each molecule. f3c mutant bone marrow showed no response to GM-CSF or IL-5, whereas IL-3 stimulation of f3c or fiIw mutant bone marrow was normal. fit mutant mice showed lung pathoiogy consisting of lymphocytic infiltration and areas resembling alveolar protelnosis, and also exhibited low basal numbers of eoslnophils. Infection of 5c mutant mice by Nippostrongyius brasiliensis resulted in the absence of blood and lung eoslnophllla. Animals repopulated with pc mutant bone marrow cells showed slower leukocyte recovery and reduced eosinophil numbers. These data define the role of 5c in vivo, and show a phenotype that is likely to be the cumulative effect of loss of GM-CSF and IL-5 stimulation.