Cachexia, defined as an accelerated loss of skeletal muscle in the context of a chronic inflammatory response, is common in rheumatoid arthritis but it has not been demonstrated in patients with ankylosing spondylitis (AS). The aim of this study was to determine muscle wasting and its functional consequences in a group of patients with well-established AS. Nineteen male patients (mean age 53 yrs) with long-standing AS (mean disease duration 19 yrs) and radiological changes (84% had one or more syndesmophytes) were compared with 19 age-matched healthy males with similar levels of habitual physical activity. Body composition was assessed by dual energy X-ray absorptiometry. Muscle strength was measured by isokinetic knee extension and hand grip dynamometry, and by 30 s arm curl and chair sit-to-stand tests. AS patients showed a statistically and clinically significant 12% reduction in arms and legs lean mass, a proxy measure of total body skeletal muscle mass, compared with healthy controls (P < 0.05). This muscle loss was significantly associated with reduced upper and lower body strength (correlation coefficients ranging between 0.37 and 0.79, P < 0.05). These results provide preliminary evidence that cachexia is a functionally relevant systemic complication of AS, particularly in patients with long-standing disease and radiological changes. Progressive resistance training and other interventions aimed at stimulating skeletal muscle growth might be beneficial in this population, and further studies on the pathophysiology of cachexia in AS patients are needed.