Mannose-binding lectin (MBL), a collagen-like serum protein, is a key component of innate immunity. MBL binding to carbohydrates present on pathogens mediates lectin-dependent activation of the complement pathway. There is growing interest in the importance of innate immunity in host defense, particularly when adaptive immunity is compromised. Three single nucleotide polymorphisms (SNPs) of the MBL gene have been described in the first exon to be associated with low MBL serum concentrations as well as impaired MBL structure and function. Clinical studies have shown that these MBL SNPs are associated with increased susceptibility to infections, especially in immunocompromised patients. To investigate the association between acute kidney transplant rejection and polymorphism at codon 54 of the MBL gene, the DNA genomic of 133 renal transplant recipients and 117 healthy blood donors was analyzed by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified into two groups: group 1 included 32 HLA-identical recipients and group 2, 101 one haplo-identical recipients. Forty-eight (36.1%) subjects had developed one or more acute rejection episodes (AREs) within the first 6 months after transplantation: 9 in group 1 (28.12%) and 39 in group 2 (38.61%). The genotype and allele frequencies of (+54) MBL gene polymorphism among patients and controls did not reveal a significant difference. However, the frequency of MBL-B mutant allele was increased among patients with AREs compared with those without AREs: group 1 (0.167 vs 0.065) versus group 2 (0.205 vs 0.105). Although the difference was not significant, perhaps because of the small number of patients, the MBL at codon (+54) polymorphism could be involved in the susceptibility of Tunisian kidney transplant recipients to acute allograft rejection episodes.