We wished to determine the extent to which respondents provided the same answers to a health-related quality of life (HRQL) questionnaire in self- and interviewer-administered forms. One hundred and fifty patients with asthma who were symptomatic or required treatment at least once a week, and had airway hyperresponsiveness to methacholine aerosol (PC20 < 8.0 mg/ml) participated. Patients completed a 152-item HRQL questionnaire in both interviewer and self-administered forms, separated by a 2-week interval, the order determined by random allocation. The percentage of items endorsed by the self-administered approach was significantly higher than that of the interviewer-administered approach overall (46.9 vs 35.8%) (p < 0.0001). The difference was consistent across all six domains; the absolute difference in the proportion of items endorsed varied from 8.9 to 12.3%. The intraclass correlations for the proportion of subjects endorsing an item was 0.84. Self- and interviewer-administered questionnaires yield very similar results in discriminating between subjects, but the self-administered version shows systematically greater HRQL impairment.