We have used the helium/oxygen technique to assess the main site of airflow obstruction in patients with asthma. Of 14 out-patients with asthma studied serially (minimum of three observations over 5-12 months) 10 remained either responders or non-responders to helium/oxygen (He/O2) on each occasion tested, despite variations in severity of airflow obstruction. Four out of six patients studied during an acute exacerbation of asthma were initially non-responders to He/O2 but became responders during recovery. The response to He/O2 of these and 15 other patients with asthma was compared with a variety of clinical features. There was a statistically significant decline in flow rate response to He/O2 breathing with increased length of history of asthma, but no differences in smoking history, are, sex or atopic status between the responders and non-responders. This implies a progressive involvement of smaller peripheral airways during the course of the disease. Perhaps more systematic treatment of young asthmatics would prevent this.