The objective of this study was to evaluate a questionnaire for assessing general and disease-specific quality of life among people with cytomegalovirus (CMV) retinitis. Cross-sectional and longitudinal analyses of data from 279 people enrolled in the CMV Retinitis Retreatment Trial were used. At baseline, Cronbach's alpha and multitrait analysis were used to assess internal consistency and discriminant construct validity for scales of general health, vision, and treatment impact. Associations of scales with clinical measures of health and vision were assessed at baseline with Pearson correlations and t tests, and over time with generalized estimating equations regression. Internal consistency coefficients ranged from .68 to.88. Criteria for discriminant validity were fulfilled for most scales; however, the general health perceptions and energy scales were highly correlated. Scales were moderately correlated with clinical measures at baseline. Over time, scale scores were associated with Karnofsky scores and clinical measures of CMV retinitis and vision. General and CMV retinitis-specific quality of life measures appear reliable, valid, and responsive.