A multistage laboratory protocol for the diagnosis of immunodeficiency is useful for the efficient identification of immunodeficient patients. The protocol presented in this article starts with the patient's clinical presentation. In the initial stages a low threshold for the performance of simple screening is applied, thus allowing early exclusion of potential immunodeficiencies, as well as identification of patients before serious infections have compromised their general condition. In the later stages, more elaborate tests leading to diagnosis and definitive classification are reserved for those few patients in whom the presence of an immunodeficiency is more probable. This definitive classification is important for the identification of carriers and for the genetic counselling of the family. The protocol described has been developed in cooperation with the Dutch national working parties of clinical immunologists (paediatric as well as internal medicine) and laboratory immunologists who are involved in diagnosing or treating patients with immunodeficiency.