AIM: To investigate the prevalence of chronic respiratory symptoms in 9 metapopulations on Adriatic islands in Croatia, and the relationship between respiratory symptoms and individual genetic background. ----- METHODS: We obtained random sample of 1001 adult inhabitants of 9 Adriatic island villages in Croatia, that also included immigrants to these villages. European Union respiratory health questionnaire and World Health Organization non-communicable diseases questionnaire were used. Personal genetic histories were reconstructed, based on the two-generation ancestral pedigrees. Bivariate and multivariate methods were used in the analysis. ----- RESULTS: Women reported the occurrence of acute dyspnea (P=0.017), cough (P=0.002), and asthma (P=0.002) more often than men. Gender was the strongest predictor for acute and/or chronic cough (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.23-2.33) and asthma (OR, 2.00; 95% CI, 1.00-4.01), whereas smoking was the strongest risk factor for acute and chronic dyspnea (OR, 1.90; 95% CI, 1.21-2.99) and airway narrowing (OR, 1.84; 95% CI, 1.18-2.87). Residence on the northern islands increased the odds of allergy, whereas the highest odds ratio of 3.20 was associated with the interaction of northern residence and immigrant background. Genetic background was a significant predictor only for the occurrence of allergy symptoms. ----- CONCLUSION: Differences in respiratory findings among the island inhabitants were often associated with smoking prevalence. Interaction of residence on northern Adriatic islands and immigrant background proved to be the strongest predictor for the occurrence of allergy symptoms. This study indicated that environmental factors played a very important role in the occurrence of respiratory symptoms.