Pulmonary surfactant protein-D (SP-D) is a multifunctional, pattern recognition molecule involved in resistance to allergen challenge and pulmonary inflammation. In view of therapeutic effects of exogenous SP-D or recombinant fragment of human surfactant protein-D (rhSP-D) (composed of eight Gly-X-Y collagen repeat sequences, homotrimeric neck and lectin domains) in murine models of lung allergy and hypereosinophilic SP-D gene-deficient mice, we investigated the possibility of a direct interaction of purified rhSP-D with human eosinophils derived from allergic patients and healthy donors. rhSP-D showed a sugar- and calcium-dependent binding to human eosinophils, suggesting involvement of its carbohydrate recognition domain. While eosinophils from allergic patients showed a significant increase in apoptosis, oxidative burst and CD69 expression in presence of rhSP-D, eosinophils from healthy donors showed no significant change. However, these eosinophils from healthy donors when primed with IL-5 exhibited increase in apoptosis on incubation with rhSP-D. Apoptosis mediated by rhSP-D in primed eosinophils was not affected by the antioxidant, N-acetyl-L-cysteine. There was a manifold increase in binding of rhSP-D to apoptotic eosinophils than the normal eosinophils and rhSP-D induced a significant increase in uptake of apoptotic eosinophils by J774A.1 macrophage cells. The study suggests that rhSP-D mediated preferential increase of apoptosis of primed eosinophils while not affecting the normal eosinophils and increased phagocytosis of apoptotic eosinophils may be important mechanisms of rhSP-D and plausibly SP-D-mediated resolution of allergic eosinophilic inflammation in vivo.