We have investigated a possible association between recurrence of otitis media and low concentrations of mannan-binding protein (MBP) in plasma and upper-airway secretions. The protein concentration was measured in plasma (n = 76), nasopharyngeal secretions (n = 83) and middle ear effusions (n = 73) from otitis-prone children, children with less recurrence of acute otitis media, children with no previous history of acute otitis media, but suffering from secretory otitis media, and healthy children. Moreover, genetic polymorphisms associated with low MBP plasma levels were investigated in DNA from nasopharyngeal tonsils of 89 children with recurrence of otitis media. A wide range of MBP plasma concentrations was found. No statistically significant differences in MBP plasma concentration were observed between patients and controls. Nor was there any increased frequency of the genotypes associated with low MBP plasma concentrations. Thus, our results do not support the assumption that low concentration and/or MBP deficiency alone predispose to recurrence of otitis media in Caucasian children. MBP was detected in both nasopharyngeal secretions (1/175 of plasma level) and middle ear effusions (1/4 of plasma level), suggesting a role for the protein in the local mucosal immune defense system at these locations. In contrast, MBP was undetectable in 53 samples of mixed-saliva.