IkappaBgamma (IkappaBgamma) is a 70-kDa protein that is encoded by the C-terminal part of the NF-kappaB p105 gene and acts as an inhibitor of the transcription factor NF-kappaB. Until now, IkappaBgamma expression has only been described in cell-culture models of B-lymphocytes and enterocytes but not in tissues. In a model of radiation-induced pulmonary damage, we found that mast cells accumulating after irradiation are the only cells in the rat lung that are positive for IkappaBgamma. The mast cells were characterised by their metachromatic staining with toluidine blue and by double immunofluorescence labelling with mast-cell tryptase. Western blotting revealed that the lung mast cells expressed the 70-kDa form of IkappaBgamma cytoplasmatically and that no alternative splicing variants were expressed. In addition, we studied 11 cases of systemic mastocytosis, as well as 5 cases of mast-cell hyperplasia. In all cases, the mast cells stained strongly with IkappaBgamma. Rat peritoneal mast cells also contained high levels of IkappaBgamma. Since NF-kappaB is an important regulator of mast-cell functions, IkappaBgamma is likely to play a central role in the maintenance of the mast-cell phenotype and possibly in the modification of mast-cell-dependent immune responses.