To compare the efficacy of various end-stage renal disease (ESRD) therapies valid and reproducible probes which measure well-being and are specific for ESRD are necessary. Four studies were undertaken to provide and test these probes. (1) 107 dialysis and 119 transplant recipients were interviewed to determine the prevalence of 24 physical symptoms. (2) A questionnaire was devised using 2 new indexes (a symptom scale derived from the first study using 12 symptoms and an affect scale comprising 12 emotions) and 6 indexes previously used in other chronic illnesses. Interobserver and intraobserver reproducibility was satisfactory. (3) Construct validity for the questionnaire was shown by interviewing 97 dialysis and 82 transplant patients in whom we hypothesized that physical well-being would be better in transplant patients. After age matching the transplant group was more active, with a higher objective quality of life and fewer physical symptoms than the dialysis group. (4) 63 stable dialysis, 67 stable transplant, 15 dialysis patients successfully transplanted in the intervening year and 5 failed transplanted patients were reinterviewed 1 year later to assess the responsiveness of the questionnaire. In the group who had recently been successfully transplanted both physical, affect and quality of life scores showed a major improvement following transplant. We conclude that this questionnaire is specific for ESRD, examines physical, psychological, and social well-being, is brief, easily administered, reproducible, has construct validity and is responsive to changes in therapy.