Childhood asthma and wheeze is more common among boys than girls, while the opposite is found in adults. The main objective was to study the incidence and the course of wheeze and asthma during adolescence with focus on gender differences. In addition, we explored associations between lifestyle factors at baseline and wheeze at follow-up. A total of 2399 adolescents answered validated questionnaires on respiratory symptoms and lifestyle in 1995-1997 (13-15 years) and at follow-up in 2000-2001 (17-19 years). The risk of reporting wheeze and asthma at follow-up was greater in girls compared to boys among subjects reporting no respiratory symptoms at baseline; Relative risk: 1.4 and 2.4, respectively. More girls than boys reported current wheeze at follow-up, both among those with current wheeze (girls 60%, boys 48%) and previous wheeze (girls 33%, boys 28%) at baseline. In girls, development of current wheeze was significantly associated with current smoking (OR=2.8) and stable current wheeze was significantly associated with overweight (OR=2.4). Similar associations were not significant in boys. More girls than boys developed wheeze, had stable wheeze or had relapse of previous symptoms during the four year follow-up. The impact of smoking and overweight may put girls at a higher risk of respiratory symptoms than boys. Awareness of the gender difference in respiratory symptoms is important for diagnosis and preventive strategies during adolescence.