Mannose-binding lectin (MBL) insufficiency due to polymorphisms in the MBL2 gene causes an opsonization defect, which has been connected to infections and atopy. We investigated the significance of MBL2 genotypes with regard to persistent asthma and atopy among adults. The genotypes were determined in 243 adults with persistent asthma and 400 controls. Atopy was determined by skin-prick test. As a result, the carriage of -221 base pairs (bp) promoter region variant allele X (nucleotide change G-->C; alleles Y-->X, respectively) causing low MBL expression proved to be a significant risk factor for asthma in non-atopic males [odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23-5.15; P = 0.01]. Furthermore, the X-allele carriage was associated with the decrease in lung function (forced expiratory volume at 1 s, FEV(1)) during follow-up in the patients with asthma (P = 0.033), the effect being strongest for non-atopic asthmatics (P = 0.042). The MBL2 genotype had no clear effect on the occurrence of atopy in adults. In conclusion, our results abrogate the previously suggested predisposing effect of MBL insufficiency on atopy at least in adults. However, as MBL is a complement component participating in immune defence against microbes, and as in the pathogenesis of non-atopic asthma infectious agents are probably involved, the gene-environment interactions between MBL and infections should be assessed further with regard to asthma.