Mannose-binding lectin (MBL) deficiency (or the common opsonic defect) has been reported as a risk factor for several immunologically controlled conditions, including infection and graft rejection. However, the effects of MBL deficiency on acute rejection after heart transplantation are unknown. Ninety heart transplant recipients were included in this study. Plasma MBL quantification was performed using a commercially available enzyme-linked immunoassay (ELISA). Acute rejection was diagnosed via endomyocardial biopsy and histologic assessment. MBL concentration was controlled for demographics, immunosuppression and anti-viral therapy. Individuals with dysfunctional MBL had significantly fewer rejection episodes (6.3 +/- 3.8%) than those with functional MBL (12.9 +/- 11.6%) (p = 0.016). We found no significant difference between MBL concentrations among those with (1,232 +/- 58 ng/ml) and those without (1,216 +/- 161 ng/ml) GCAD (p = 0.841). There was also no significant difference between the incidence of GCAD in those with "normal" concentrations (p = 0.782). Heart transplant recipients with MBL deficiency had fewer acute graft rejection episodes compared to patients with functional MBL. This suggests the lectin pathway of complement activation is an important process in graft rejection. Furthermore, functional MBL may indicate a greater likelihood of rejection.