Surfactant protein D (SP-D) interacts with various different microorganisms and plays an important role in pulmonary innate immunity. SP-D expression has also been detected in extrapulmonary tissues, including the gastro-intestinal tract. However, its function in the intestine is unknown and may differ considerably from SP-D functions in the lung. Therefore, the effects of porcine SP-D (pSP-D) on several strains of intestinal bacteria were studied by means of bacterial growth assays, colony-count assays, radial diffusion assays and differential fluorescent staining. Furthermore, the effect of pSP-D on the adhesion- and invasion-characteristics was investigated. All bacterial strains tested in this study were aggregated by pSP-D, but only Escherichia coli K12 was susceptible to pSP-D-mediated growth inhibition. Bacterial membrane integrity of E. coli K12 was affected by pSP-D, but this did not lead to a reduced bacterial viability. Therefore, it is unlikely that pSP-D has a direct antimicrobial effect, and the observed effects are most likely due to pSP-D-mediated bacterial aggregation. The effects of pSP-D on bacterial adhesion and invasion were studied with the porcine intestinal epithelial cell line IPI-2I. Preincubation with pSP-D results in a several-fold increase in adhesion (E. coli and Salmonella) and invasion (Salmonella), but did not affect the IL-8 production induced by the bacteria. Results obtained in this study suggest that pSP-D promotes uptake of pathogenic bacteria by epithelial cells. This may reflect a scavenger function for pSP-D in the intestine, which enables the host to generate a more rapid response to infectious bacteria.