BACKGROUND The extent to which maternal smoking in pregnancy (MSP) has persisting effects on respiratory health remains uncertain and the mechanisms involved are not fully understood. Alterations in immune function have been proposed as a mechanism contributing to respiratory disease. OBJECTIVE To determine whether MSP increases risk of respiratory disorders in adolescence and, if so, whether this occurs by decreased lung function, altered immune function, and/or enhanced atopy. METHODS Data on spirometry, bronchial responsiveness, respiratory symptoms, total and allergen-specific IgE and IgG4, immune function, and inflammatory markers were obtained from 1,129 participants in the 14-year follow-up of the Western Australian Pregnancy (Raine) Cohort and related to MSP using regression analyses. RESULTS MSP was reported for 21.0% (237 of 1,129) of participants, with 92 (8.1%) reporting current smoking. MSP was associated with some altered immune measures at age 14. MSP was strongly related to reduced lung function in current nonsmokers (forced expiratory flow midexpiratory phase [FEF25-75%], P = 0.016; FEV1/FVC, P = 0.009) and increased risk for current asthma (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.16-2.92; P = 0.01), current wheeze (OR, 1.77; 95% CI, 1.14-2.75; P = 0.011), and exercise-induced wheeze (OR, 2.29; 95% CI, 1.37-3.85; P = 0.002), but not for bronchial hyperresponsiveness or atopy. Adjustment for immune measures and/or lung function in multivariate models did not greatly alter these associations and the increased risks for asthma and wheeze were not modified by sex, atopy, or maternal history of asthma or atopy. CONCLUSIONS MSP increases risk of asthma and wheezing in adolescence; mechanisms go beyond reducing lung function and exclude altering immune function or enhancing atopy.