Abnormalities of the local defense mechanisms of the upper airways are very common, but severe (inherited) diseases are rare. The most important ones are humoral immune deficiencies, cystic fibrosis and primary ciliary dyskinesia. In differentiating these diseases the clinical picture is essential, giving clues to each of the diseases. Additional investigations are indicated whenever common diseases such as allergy, gastro-esofageal reflux and adenoid hypertrophy cannot explain the problems. With a battery of tests including immunoglobulin measurements, sweat test and ciliary investigations in the majority of cases the explanation can be found.