We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis. We further postulated that chronic GVHD, whatever its cause, involves thymic epithelium as a target organ. When tested 11 mo or more posttransplant, patients with chronic GVHD had lower absolute FTS levels (p less than 0.02) and lower age-corrected levels (p = 0.05) than patients without chronic GHVD. Low values in chronic GVHD were associated with the disease itself and not its therapy. These findings show that thymic epithelial secretory function is impaired in chronic GVHD, and this may in part be responsible for the immunodeficiency characteristic of these patients.