OBJECTIVE: The PedsQL (Pediatric Quality of Life Inventory) is a modular instrument designed to measure health-related quality of life (HRQOL) and disease-specific symptoms in children and adolescents ages 2-18. The new PedsQL Infant Scales were designed as a generic HRQOL instrument specifically for healthy and ill infants ages 1-24 months. The objective of this study was to report on the initial feasibility, internal consistency reliability, and validity of the PedsQL Infant Scales in healthy, acutely ill, and chronically ill infants. METHODS: The 36-item (ages 1-12 months) and 45-item (ages 13-24 months) PedsQL Infant Scales (Physical Functioning, Physical Symptoms, Emotional Functioning, Social Functioning, Cognitive Functioning) were completed by 683 parents of healthy, acutely ill, and chronically ill infants. RESULTS: The PedsQL Infant Scales evidenced minimal missing responses, achieved excellent internal consistency reliability for the Total Scale Scores (alpha = 0.92), distinguished between healthy infants and acutely and chronically ill infants, and demonstrated a confirmatory factor structure largely consistent with the a priori conceptual model. CONCLUSIONS: The results demonstrate the initial measurement properties of the PedsQL Infant Scales in healthy and ill infants. The findings suggest that the PedsQL Infant Scales may be utilized in the evaluation of generic HRQOL in infants ages 1-24 months.