We investigated the prognostic value of cytotoxic T-lymphocyte precursor frequencies (CTL-p-f) for the development of graft-versus-host disease (GvHD) in a cohort of 92 recipients of a hematopoietic stem cell transplantation from HLA-matched sibling donors. CTL-p-f and clinical variables were correlated with acute GvHD and chronic GvHD in univariate and multivariate analyses. CTL-p-f resulted an independent risk factor for severe acute GvHD. Moreover, a trend towards a correlation between CTL-p-f and chronic GvHD was observed. In summary CTL-p-f may be considered as a functional assay useful for identifying patients at high risk of severe GVHD.