Attempts to identify an early and discriminating marker of acute graft-versus-host disease (aGvHD) have been unsuccessful. The levels of soluble CD4 and soluble CD8 in serum correlate with T cell subset activation and may be important in monitoring and characterizing immunological processes. We determined serum soluble CD4 (sCD4) and sCD8 levels with a two-site sandwich enzyme immunoassay on patients' serum samples collected prior to bone marrow transplantation and weekly after transplantation until day +28. No significant increment of sCD4 was documented in each determination. sCD8 rose significantly before diagnosis or development of maximal clinical symptoms in patients with grade II-III aGvHD than grade 0-I aGvHD [at day +21--median value 447 IU/ml; range 94-713; versus 1136 IU/ml, range 790-1416 (P = 0.002); at day +28--median value 443 IU/ml, range 73-992, versus 1164 IU/ml, range 625-1960 (P = 0.005)]. On the day of marrow infusion the sCD8 levels were significantly higher in patients who subsequently developed grade II-III than in patients with grade 0-I aGvHD (median value 155 IU/ml, range 10-332, versus 350 IU/ml, range 283-830; P = 0.003). Careful monitoring of sCD8 is a useful tool for a prompt aGvHD diagnosis and may be used in a clinical bone marrow transplantation setting.