BACKGROUND: Various volatile organic compounds (VOCs) have been related to respiratory health effects, but have generally been assessed individually without taking into account the fact that such pollutants are highly correlated to one other. AIMS: We investigated the effects of exposure to various VOC, and considered their combined effect on adult asthma and rhinitis. METHOD: A national cross-sectional representative survey conducted by the Indoor Air Quality Observatory objectively assessed 20 VOCs in 490 main dwellings in France. A standardized questionnaire determined the prevalence of asthma and rhinitis among 1012 inhabitants of the dwellings (≥ 15 years). Marginal models for binary outcome were used to relate VOCs exposure to asthma and rhinitis, controlling for potential confounders. A global score representing the number of VOCs in each dwelling with an elevated concentration (using the 3(rd) quartile value of the distribution as a threshold value) was then derived as a measure of the combined effect of VOCs. Specific scores were built using a similar approach, grouping VOCs by family. RESULTS: Asthma (8.6%) was significantly associated with N-undecane and 1,2,4-trimethylbenzene and rhinitis (38.3%) with ethylbenzene, trichloroethylene, m/p- and o-xylene. The global VOC score was associated with a significant risk of asthma and rhinitis (odds ratio (OR) of 1.40 and 1.22, respectively, for 5 additional VOCs with high exposure level). Both specific scores for aromatic hydrocarbons and aliphatic hydrocarbons were associated with a significantly risk of asthma (OR=1.12; 95% confidence interval (CI): 1.01-1.24 and OR=1.41; 95% CI=1.03-1.93, respectively). The specific VOC score for halogenated hydrocarbons was associated with a significant risk of rhinitis (OR=1.28; 95% CI: 1.07-1.54). CONCLUSION: We have shown that high concentrations of VOCs in homes were associated with an increasing prevalence of asthma and rhinitis in adults.