The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed intracellular calcium release channel composed of four ∼300kDa subunits. Calcium signalling mediated via the IP3R and the related ryanodine receptor (RyR) is involved in numerous cellular processes including fertilisation, gene transcription, neurotransmitter release and muscle contraction. Recently, we presented evidence that the RyR2 N-terminus self-associates into a tetrameric form, which stabilises the closed conformation of the channel. Given that the IP3R and RyR amino-termini have a high degree of similarity in both their protein sequence (∼40%) and three-dimensional structure, we investigated the oligomerisation properties of the IP3R N-terminus. A type 1 IP3R fragment (residues 1-667) was expressed in mammalian HEK293 cells and subjected to chemical cross-linking. We found that the IP3R1 N-terminal fragment is capable of oligomerisation, forming predominantly tetramers. The presence of a 15 amino acid splice insertion or of the cognate ligand, IP3, did not affect tetramerisation. The IP3R1 N-terminus self-interaction was further verified by co-immunoprecipitation assays. These studies indicate the putative involvement of the N-terminal region in IP3R1 oligomerisation. It is therefore possible that, in addition to its direct role in ligand binding, the IP3R1 N-terminus is involved in regulation of the channel via inter-subunit interactions and that these two processes may be directly linked.