OBJECTIVE: To evaluate the outcome of a multidisciplinary treatment programme for patients with chronic fatigue syndrome, including health-related quality of life (HRQoL) and psychosocial variables, and exercise capacity measures. DESIGN: A six-month prospective outcome study. SETTING: University outpatient rehabilitation clinic; group setting. SUBJECTS: One hundred and sixteen women fulfilling chronic fatigue syndrome criteria. INTERVENTIONS: Cognitive behaviourally and graded exercise-based strategies; emphasis on adaptive lifestyle changes. MEASURES: Short Form General Health Survey (SF-36); Symptom Checklist (SCL-90); Causal Attribution List (CAL); Self-Efficacy Scale (SE); maximum progressive bicycle ergometer test with respiratory gas analysis; and isokinetic leg strength test, before and after treatment. RESULTS: The total group significantly improved on nearly all reported HRQoL/psychosocial variables. Changes in exercise capacity measures were rather modest and did not correlate or only weakly correlated with HRQoL/psychosocial variables. Subgroup analyses indicated that less fit patients improved significantly more on exercise capacity measures than their more fit counterparts. Patients who were fitter at baseline scored better on pretreatment HRQoL/psychosocial variables, but both subgroups improved similarly on these variables. CONCLUSIONS: Health-related quality of life and psychosocial functioning in patients with chronic fatigue syndrome improves after a six-month cognitive behaviourally and graded exercise-based multidisciplinary treatment programme. Increase in exercise capacity measures is not a necessary condition for reported improvements, except for less fit patients.