Obliterative bronchiolitis (OB) is a major complication of lung transplantation, affecting about 50% of patients who survive beyond 3 months. The murine heterotopic tracheal transplantation model has been developed for investigation of the etiology, pathogenesis and prevention of OB. Previous data showed no differences between different sites of tracheal graft implantation, but did not study an intramuscular placement. This pilot study compared 2 sites of heterotopic tracheal allograft transplantation in mice. Donor-recipient strain combinations were completely disparate across MHC and minor antigens. 16 C3H/He (C3H;H-2) mice received tracheal grafts from C3H donors (isograft) and BALB/c (BALB;H-2) donors (allografts) implanted without primary vascularization in a dorsal subcutaneous pouch (SC) (n=5), or within the pectoralis major muscle (IM) (n=11). Six C3H mice were recipients of tracheal grafts from C3H, BALB, and C57BL/6 (B6; H-2) implanted in the dorsal SC position. All grafts were removed 28 days after transplantation and examined for microscopic evidence of acute and chronic rejection. No isografts showed rejection. Mean luminal occlusion in BALB allografts placed in the IM site was 35.5% comparede to 86.0% for BALB allografts in the SC position (P<0.0008). In animals that received multiple grafts. Mean luminal occlusion of BALB allografts was 80%, however B6 allografts showed much less occlusion: 5.3% (P<0.0007). In conclusion, in contrast to previous data, our pilot data suggest that site of airway allograft implantation affects obliterative bronchiolitis development. Although isografts showed no apparent differences between implantation sites, allografts implanted in the IM site showed significantly less occlusion compared to SC implantation. Possibly due to rich muscle blood circulation, supporting of role of ischemia as a predisposing factor in development and progression of OB. In contrast to BALB allografts, B6 allografts showed significantly less occlusion by day 28, reflecting possible strain-related differences in immunogenicity.