Most individuals with AAT deficiency have escaped detection by healthcare systems worldwide. The large number of undiagnosed individuals has made it difficult to define the natural history of the clinical disease accurately, and severe ascertainment bias has colored the clinical descriptions of the disease. Most importantly, undetected individuals lose opportunities for important lifestyle changes and preventive therapies. To address this problem, the World Health Organization has recommended that all patients with chronic obstructive lung disease, and all adults and adolescents with asthma, be tested for AAT deficiency. Historically, the AAT Deficiency Detection Center has tested more than 30 000 individuals for the disease, and we have identified more than 1000 cases of AAT deficiency (approximately 30% of the known cases in the United States). Currently, we are implementing methods for determining AAT concentration (level), phenotype, and genotype in specimens of whole blood dried onto filter paper. This full spectrum of robust tests is performed on samples that are easily obtained and shipped to a central laboratory for processing. Wide application of these procedures may help to bring large numbers of presently undiagnosed patients to medical attention.