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Background: The cysteine protease inhibitor cystatin C may play a role in the development and progression of abdominal aortic aneurysms (AAAs). Methods: From a mass screening trial of men aged 65–73 years, 151 small AAAs were followed for a mean of 2·9 years. Of these patients, 142 had serum samples taken to determine the levels of cystatin C, creatinine and C-reactive protein (CRP). Results: Serum cystatin C concentration correlated negatively with AAA size (r = - 0·22 (95 per cent confidence interval (c.i.) - 0·59 to - 0·02)) and annual expansion rate (r = - 0·24 (95 per cent c.i. - 0·75 to - 0·05)), persisting after adjustment for renal function, smoking, diastolic blood pressure, CRP, age and AAA size. Creatinine clearance and CRP did not correlate with size or expansion rate. Thirty-one AAAs had expanded to over 50 mm, when operation was recommended. The serum level of cystatin C was a significant predictor of this occurrence, with a sensitivity and specificity of 61 and 57 per cent respectively. However, initial AAA size had the optimal sensitivity and specificity (both 81 per cent) in this regard. Conclusion: Deficiency of cystatin C was associated with increased aneurysm size and expansion rate, possibly due to lack of inhibition of cysteine proteases. [ABSTRACT FROM AUTHOR]