When a randomized trial (NMSG 4/90) comparing treatment with melphalan/prednisone to melphalan/ prednisone + interferon alpha-2b in newly diagnosed multiple myeloma was initiated in 1990, a quality-of-life assessment was integrated into the study. We used the questionnaire (QLQ-C30) developed by the European Organization of Research and Treatment of Cancer (EORTC) Study Group on Quality of Life. The QLQ-C30 incorporates five functional scales, three symptom scales, a global health and quality-of life scale and some single symptom measures. The questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48 months. 524 (90.2%) of 581 patients enrolled in the NMSG 4/90 completed the first questionnaire, and 484 (83.3%) completed all questionnaires given to them. All but one of the scales met the minimum criteria of reliability (Cronbach's alpha >/ 0.70). Validity was shown by (1) the ability of the scales to discriminate clearly between patients differing in clinical status as defined by pretreatment W.H.O. performance index and Durie & Salmon stage, and (2) the sensitivity to changes in objective disease status (response and relapse). This is the first report of the measurement of health-related quality of life in a prospective clinical trial in multiple myeloma. The results demonstrate that the QLQ-C30 is a reliable and valid instrument for the measurement of quality of life in these patients. The data will be used for a cost-utility analysis of the results of the NMSG 4/90 trial.