We performed analyses to examine the structure, validity, and responsiveness to change of the Marks Asthma Quality of Life Questionnaire (AQLQ), originally validated in Australia in a self-administered format, among 539 U.S. subjects with asthma. Subjects were interviewed twice by telephone over an 18-month period. Based on factor analyses, the subscale structure of the AQLQ was modified slightly to eliminate item overlap among subscale scores. Cross-sectionally, total AQLQ scores were significantly correlated in expected directions with baseline asthma severity scores (r = 0.58), SF-36 physical (r = -0.66) and mental (r = -0.40) health status scores, and pulmonary function (FEV1% predicted, r = -0.14). Longitudinally, changes in AQLQ total and subscale scores were significantly (P<0.01) associated with changes in asthma severity and both physical and mental status. The AQLQ, administered by telephone, appears to be useful for assessing changes in the impact of adult asthma.