We report results from the first data collection on an ongoing longitudinal study aimed at describing the natural history of adaptation to childhood epilepsy and asthma in children and their families. We studied 136 children with epilepsy and 134 children with asthma aged 8-12 years. Data were collected from the children, their mothers, and their school teachers through interviews, school records, and questionnaires. The two samples were compared on four domains of quality of life: physical, psychological, social, and school. Data were analyzed by a 2 x 2 between-subjects multivariate analysis of covariance with type of illness (epilepsy or asthma) as the independent variable and length of time since onset of illness as a covariate. A significant main effect was noted for illness [multivariate F (15, 236) = 11.36, p < 0.001]. Our major finding was that children with epilepsy had a relatively more compromised quality of life in the psychological, social, and school domains. In contrast, children with asthma had a more compromised quality of life in the physical domain. Our findings suggest that attention simply to seizure control in the clinical setting will not address the full range of quality-of-life problems of children with epilepsy.