To date, 12 secreted phospholipases A₂ (sPLA₂s) have been identified in the mouse species and divided into three structural collections (I/II/V/X, III, and XII). On the basis of their different molecular properties and tissue distributions, each sPLA₂ is likely to exert distinct functions by acting as an enzyme or ligand for specific soluble proteins or receptors, among which the M-type receptor is the best-characterized target. Here, we present the properties of binding of the full set of mouse sPLA₂s to the mouse M-type receptor. All enzymes have been produced in Escherichia coli or insect cells, and their properties of binding to the cloned and native M-type receptor have been determined. sPLA₂s IB, IIA, IIE, IIF, and X are high-affinity ligands (K_0.5 = 0.3−3 nM); sPLA₂s IIC and V are low-affinity ligands (K_0.5 = 30−75 nM), and sPLA₂s IID, III, XIIA, and XIIB bind only very weakly or do not bind to the M-type receptor (K_0.5 > 100 nM). Three exogenous parvoviral group XIII PLA₂s and two fungal group XIV sPLA₂s do not bind to the receptor. Together, these results indicate that the mouse M-type receptor is selective for only a subset of mouse sPLA₂s from the group I/II/V/X structural collection. Binding of mouse sPLA₂s to a recombinant soluble mouse M-type receptor leads in all cases to inhibition of enzymatic activity, and the extent of deglycosylation of the receptor decreases yet does not abolish sPLA₂ binding. The physiological meaning of binding of sPLA₂ to the M-type receptor is discussed on the basis of our current knowledge of sPLA₂ functions.