The parasite Leishmania, which causes the debilitating disease leishmaniasis, is spread by sandflies and affects millions of people around the world. It mostly reproduces asexually; however, transient fusion and genetic exchange between parasites in the sandfly gut has been observed. Serafim et al. now show that Leishmania mating clumps (LMCs), which facilitate parasite genetic exchange, can be induced by incubating the parasite with serum from Leishmania-naive animals. They found that pentameric natural IgM (IgMn), which binds to components of the microbial cell wall with low affinity and is taken up with every sandfly blood meal, binds the parasites and initiates the formation of LMCs in the sandfly gut. Moreover, binding to IgMn activates translational and transcriptional machinery in clumped parasites that likely promotes Leishmania fusion and hybrid formation. These findings provide insights into the relationship between a blood-feeding insect vector, a parasite and a mammalian host, and sheds light on the mechanisms that promote Leishmania diversity in nature.