We used differential display, a method designed to amplify partial cDNA sequences from subsets of mRNAs, to identify mRNAs induced by ionizing radiation in human Epstein Barr Virus (EBV)-transformed lymphoblastoid cells. Increased expression of a cDNA corresponding to the inositol 1,4,5 trisphosphate receptor (InsP3R) type 1 was observed after exposure of cells to 3Gy gamma-rays. This was confirmed by Northern blot analysis. The increase in mRNA for InsP3R type 1 was accompanied by a corresponding increase in the level of InsP3R type 1 protein as determined by Western blotting. Exposure of cells from patients with the human genetic disorder ataxia-telangiectasia (A-T), characterized by hypersensitivity to ionizing radiation, failed to change the levels of InsP3R type 1 mRNA and, as expected, there was no increase in InsP3R type 1 protein in A-T cells in response to radiation exposure. Protein levels for two other InsP3Rs, types 2 and 3, were observed to increase in control and A-T cells after exposure to ionizing radiation. The induction of the InsP3R type 1, which is primarily located in the endoplasmic reticulum, may play an important role in radiation signal transduction.