We examined the effects of active untreated chronic lymphocytic leukaemia (CLL) on health-related quality of life (HRQoL), measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) at randomisation into the Leukaemia Research Fund CLL4 trial. Patients were scored 0-100 within each of 15 domains. A difference between groups of > or = 10 points was deemed clinically significant (asterisked * below). 431 valid baseline questionnaires were returned. Compared with population norms, patients had impaired HRQoL in 13/15 domains. The greatest differences were in fatigue*, sleep disturbance*, role functioning and global HRQoL. Fatigue was reported by 81% of patients, compared with the next most common symptoms: sleep disturbance (56%) and dyspnoea (49%). There was no association between spleen, liver or lymph node enlargement, or lymphocytosis and any HRQoL domain. Older age (> or =70 years) was associated with poorer physical functioning (P < 0.001) but fewer financial difficulties (P < 0.001*). Impairment of HRQoL at baseline was most apparent in stage A-progressive patients with B-symptoms and stage C patients with haemoglobin <120 g/l: compared with all others, these patients had poorer physical, role and social functioning, more fatigue and dyspnoea and poorer global HRQoL (all P < or = 0.001*). These findings support the recommendation to begin treatment when patients experience symptomatic disease, to improve HRQoL.