Objectives: To evaluate the feasibility of measuring habitual physical activity (HPA) in children with cystic fibrosis (CF)-and to assess the relation between HPA and the rate of decline in FEV1 over a period of 2 years. Study design: At regular clinic visits, 109 patients (7 to 17 years; 56 girls) performed pulmonary function testing and completed the Habitual Activity Estimation Scale (HAES). Patients were divided into quartiles, based on activity levels derived from the HAES. Results: Girls in the two lowest activity quartiles had a more rapid rate of decline FEV1 (-3.40% and -3.05% predicted, respectively) than girls in the two highest activity quartiles (-0.93% and + 1.17% predicted, respectively) (P = .02). In boys, the rate of decline of FEV1 was similar in all activity quartiles (-1.95% predicted). Patients reported significantly more activity in summer compared with spring, winter, and fall (P < .0001), and boys reported greater activity than girls (6.5 ± 2.9 vs 5.4 ± 2.5 h/d, P < .05). Conclusions: The annual rate of change of FEV1 was related to activity quartile in girls but not in boys. This research suggests that an inactive lifestyle may partially explain the poorer survival of female patients with CF. The HAES is a feasible tool for routine follow-up of HPA in our CF clinic. Objectives: To evaluate the feasibility of measuring habitual physical activity (HPA) in children with cystic fibrosis (CF) -and to assess the relation between HPA and the rate of decline in FEV1 over a period of 2 years. Study design: At regular clinic Girls were divided into quartiles, based on activity levels derived from the HAES. Results: Girls in the bottom of the two Rates (HAES) activity quartiles had a more rapid rate of decline FEV1 (-3.40% and -3.05% predicted, respectively) than girls in the two highest activity quartiles (-0.93% and + 1.17% predicted, respectively) (P = .02). In boys, the rate of decline of FEV1 was similar in all activity quartiles (-1.95% predicted). Patients reported significantly more activity in summer compared with spring, winter, and fall (P <.0001), and boys reported greater activity than girls (6.5 ± 2.9 vs 5.4 ± 2.5 h / d, P <.05). Conclusions: The annual rate of change of FEV1 was related to activity quartile in girls but not in boys. This research suggests that an inactive lifestyle may partially explain the poorer survival of female patients with CF. The HAES is a feasible tool for routine follow-up of HPA in our CF clinic.