Mannose-binding lectin (MBL) mediates important functions within the innate immune system, and its deficiency was associated with infectious complications. However, in adults without concomitant immunodeficiency the clinical relevance of MBL deficiency remains controversial. We analyzed the distribution of MBL deficiency and its association with concomitant immunodeficiency in 228 adult Caucasian patients with a history of recurrent and/or severe infections. Two hundred forty-one unrelated Caucasians without recurrent or severe infections served as control subjects. The frequency of severe MBL deficiency (plasma levels <or= 50 ng/ml) was significantly higher in patients with a history of recurrent and/or severe infections (p < 0.05, odds ratio 2.1, 95% confidence interval 1.1-4.1), and this association was independent of concomitant antibody or cellular immunodeficiency. Our data challenge the view that MBL deficiency in adulthood becomes relevant only in individuals who are immunocompromised for other reasons.