OBJECTIVES: To investigate socioeconomic variation in participation in flexible sigmoidoscopy (FS) screening for colorectal cancer. DESIGN: A prospective study nested within a multicentre randomised controlled trial of the efficacy of FS screening for the prevention and early detection of colorectal cancer (the UK flexible sigmoidoscopy trial). SETTING: Glasgow, Scotland. PARTICIPANTS: 55–64 year old adults, registered with general practitioners participating in the FS trial. MAIN OUTCOME MEASURES: Screening participation measured at three levels: questionnaire return; interest in screening; attendance at screening. RESULTS: Socioeconomic deprivation was a strong predictor of participation. Return of the screening questionnaire, expression of interest in screening, and attendance at the test, were all lower in more deprived groups. CONCLUSIONS: These results highlight the need to consider ways to reduce inequalities in screening uptake, in parallel with the introduction of any new screening programmes, to avoid exacerbating social gradients in cancer mortality.