Chronic GVHD (cGVHD) affects 30% to 90% of surviving allogeneic transplant recipients. Thus far, no quality-of-life instruments have been developed to measure the effect of this common complication of allogeneic transplantation on patients' functioning and well-being. Using a prospective cohort of 107 patients with active cGVHD who completed the symptom scale at enrollment and at intervals of 3 and 6 months, we developed a 30-item symptom scale with 7 subscales to capture the cGVHD-specific symptom burden. The symptom scale correlated highly with patients' self-assessed mild, moderate, and severe cGVHD manifestations in cross-sectional analysis. Reliability (Cronbach's alpha = 0.79-0.90), test-retest (r2 = 0.28-0.93), and convergent and discriminant validity compared to the Medical Outcomes Study Short Form 36 (SF-36) and Functional Assessment of Chronic Illness Therapy with BMT subscale (FACT-BMT) were assessed and found to be adequate. Longitudinal assessments showed that changes in overall health status correlated best with changes in quality of life as measured by the SF-36 and FACT-BMT. In contrast, changes in cGVHD severity were best detected by changes in the symptom scale. We recommend that either the SF-36 or the FACT-BMT be combined with a cGVHD-specific symptom scale to measure the impact of cGVHD on patients' quality of life and that this endpoint be included in clinical trials testing cGVHD interventions. The cGVHD symptom scale is a short, simple, and valid measure of cGVHD manifestations and can be used to follow complication-specific symptoms using patient self-administered questionnaires.