The purpose of this study was to examine relationships between patient- and disease-related variables and health-related quality of life (HQL). This cross-sectional study surveyed adults with asthma enrolled in a managed care organization (MCO). Data were obtained from a mailed questionnaire and the MCO's patient and claims databases. The Asthma Quality of Life Questionnaire (AQLQ) and the SF-36 instruments were used. The behavioral Model of Health Services Utilization was used to characterize independent variables and their relationships to HQL. Independent variables included predisposing (age, gender, education, race, number of comorbidities, years with asthma, social support, health-belief questions); enabling (income, number of metered dose inhaler (MDI) instructors, perceived inconvenience of accessing the physician); and illness level (perceived and symptom-derived asthma severity). Multivariate linear regression models were developed to examine the relationships between the independent variables and the domain and summary scores of the AQLQ and the SF-36. The survey response rate was 63% (n=603). for the AQLQ, symptom-derived severity, perceived severity, education level, and the health-belief factor Barriers were significant in all five models. Symptom-derived severity had consistently higher standardized regression coefficients than perceived severity. Barriers had the highest coefficient in all but the Symptoms domain model. Number of Comorbidities was significant in all eight domain and two summary score SF-36 models. Symptom-derived and/or perceived severity were also significant in all but the Mental Health domain model. Other frequently significant variables included the health-belief factor Barriers and Yearly Household Income. When assessing HQL of a population, such as this group of patients with asthma, one must consider patient and disease variables that may influence the results.