Activated cytotoxic T lymphocytes and natural killer cells, which are involved in the pathogenesis of GVHD and viral infections after SCT produce granzymes (Grs). This study performed an ELISA in the serum of 86 patients at various time points before and after Allo-SCT to investigate GrA and GrB levels as potential markers for these serious complications. The increase in Gr levels from the day of transplantation until the appearance of the complication was highly predictive. If GrA increased to three times its pretransplant level, the cumulative incidence of developing acute GVHD was 73% and for CMV infection 68%, in comparison with 45 and 35%, respectively, for patients without these complications. A strong increase in GrA level correlated with clinical severity of acute GVHD. No correlation was observed with early relapse or long-term overall survival. In addition to clinical parameters, a strong increase in GrA levels was identified as an independent marker for the occurrence of acute GVHD as well as for CMV infection. Similar effects were observed with GrB. In conclusion, Gr protein levels can also be used as a marker for complications after Allo-SCT.