Studies requiring the collection of biological specimens are often difficult to perform and costly. We compare face-to-face and telephone interviews to determine which is more effective for return of self-collected rectal swabs from subjects living in rural and semi-rural areas of Ontario, Canada. People interviewed face-to-face in 2006-2007 were asked to provide a rectal swab while the interviewer waited. Those interviewed by telephone were sent a package and asked to return the swab by mail, with one follow-up reminder call. Telephone interviewing resulted in a higher response rate for the completion of household and individual-level questionnaires. However, face-to-face interviews resulted in a significantly higher proportion of interviewees who returned swabs making the participation rate higher for this mode of contact (33.7 versus 25.0 percent). Using multivariable logistic regression, higher rates of rectal swab return were associated with face-to-face interviewing while adjusting for the impact of household size and respondent age and sex. For studies requiring the submission of intimate biological samples, face-to-face interviews can be expected to provide a higher rate of return than telephone interviews.