Sympathetic fibre innervation of the damaged region following injury represents a conserved event of wound healing. The present study tested the hypothesis that impaired scar healing in post-MI rats was associated with a reduction of sympathetic fibres innervating the infarct region. In 1-week post-MI rats, neurofilament-M immunoreactive fibres (1116±250 µm²/mm²) were detected innervating the infarct region and observed in close proximity to a modest number of eNOS immunoreactive scar-residing vessels. Dexamethasone treatment (6 days) of post-MI rats led to a significant reduction of scar weight (dexamethasone+MI, 38±4 versus MI, 63±2 mg) and a disproportionate non-significant decrease of scar surface area (dexamethasone+MI, 0.54±0.06 versus MI, 0.68±0.06 cm²). In dexamethasone-treated post-MI rats, the density of neurofilament-M immunoreactive fibres (125±47 µm²/mm²) innervating the infarct region was significantly reduced and associated with a decreased expression of nerve growth factor (NGF) mRNA (dexamethasone+MI, 0.80±0.07 versus MI, 1.11±0.08; p<0.05 versus MI). Previous studies have demonstrated that scar myofibroblasts synthesize NGF and may represent a cellular target of dexamethasone. The exposure of 1^st passage scar myofibroblasts to dexamethasone led to a dose-dependent suppression of ³H-thymidine uptake and a concomitant attenuation of NGF mRNA expression (untreated, 3.47±0.35 versus DEX-treated, 2.28±0.40; p<0.05 versus untreated). Thus, the present study has demonstrated that impaired scar healing in dexamethasone-treated post-MI rats was associated with a reduction of neurofilament-M immunoreactive fibres innervating the infarct region. The attenuation of scar myofibroblast proliferation and NGF mRNA expression may represent underlying mechanisms contributing to the diminished neural response in the infarct region of dexamethasone-treated post-MI rats.