Triggering receptors expressed on myeloid cells (TREM) are a family of recently discovered receptors that play important roles in innate immune responses, such as to activate inflammatory responses and to contribute to septic shock in response to microbial-mediated infections. To date, two TREM receptors in human and several homologs in mice have been identified. We report the 2.6 Å resolution crystal structure of the extracellular domain of human TREM-1. The overall fold of the receptor resembles that of a V-type immunoglobulin domain with differences primarily located in the N-terminal strand. TREM-1 forms a "head-to-tail" dimer with 4100 Å 2 interface area that is partially mediated by a domain swapping between the first strands. This mode of dimer formation is different from the "head-to-head" dimerization that existed in VHV L domains of antibodies or V domains of T cell receptors. As a result, the dimeric TREM-1 most likely contains two distinct ligand binding sites.