Functional IP3-sensitive intracellular Ca2+ release channel is considered to be a tetramer of IP3R. Heterooligomeric complexes composed of distinct types of IP3R have been reported, however, crucial evidences for them being tetramer have not appeared. Here we report that the heterooligomer composed of IP3RI and IP(3)R2 also exists as tetramer. Cross-linked heterooligomer was immunoprecipitated with IP(3)R1-specific antibody and detected by agarose-PAGE/Western blot analysis with IP(3)R2-specific antibody. Tetramer, trimer, dimer, and possibly monomer were detected. The trimer, dimer, and monomer mere Likely to be originated from the tetramer, since: (1) the immunoprecipitating antibody (IP(3)R1-specific) does not recognize IP(3)R2, therefore IP(3)R2 monomer itself could not have been immunoprecipitated; and (2) tetramer was the major native product of IP3R complex containing type 2 isoform in liver membrane fraction. Thus we conclude tetramer is the native form of heterooligomer composed of IP(3)R1 and IP(3)R2.