Children with recurring and often invasive infections with Streptococcus pneumoniae, Staphylococcus aureus and other pyogenic bacteria can be suspected of having a congenital deficiency in IRAK4, an intracellular kinase associated with Toll-Like Receptor and Interleukin-1 Receptor pathways. Febrile response is reduced and failure of leukocyte response to bacterial endotoxin and Interleukin 1 can be demonstrated in vitro. Leukocyte counts are normal. Infections can be peripheral (e.g. tonsillitis, otitis media) or invasive (e.g. meningitis, arthritis, abdominal abscess) and may be life-threatening. In surviving patients the susceptibility decreases with age and the risk of invasive infections appears to disappear by adolescence or adulthood.