Adult S.mansoni digest large amounts of host hemoglobin and release toxic heme inside their guts. We have demonstrated that free heme in S.mansoni is detoxified through its crystallization into hemozoin (Hz). Here we investigated the process of Hz formation in this parasite. Observation of both females and males worms by transmission electron microscopy showed the presence of inumerous electro-luscent round structures, similar to lipid droplet particles (LDP), in which crystalline assemblies grow on their surface. Interestingly, some of the LDPs were also found inside the gut epithelial cells (GEC), indicating that these structures were produced by GEC and further released to the gut lumen. Whole regurgitate of both males and females of unisexual and bisexual S.mansoni were capable to promote heme crystallization in vitro, but this activity was higher in females from bisexual infections. Lipid extracted from whole female regurgitates was capable to promote heme crystallization in vitro which was inhibited by two quinoline antimalarials, quinine and amodiaquine. Lipid analysis from total female regurgitates by thin layer chormatography revealed that the major neutral lipids were hydrocarbonates, cholesterol ester, cholesterol and triacylglycerol, whereas phospholipids were phosphatidylcholine and phosphatidylethanolamine. Separation of whole regurgitates in sucrose gradient produced different fractions and most of the Hz formation activity was concentrated in the lower density ones, which practically do not contain Hz. Moreover, addition of DMSO 5% promoted spontaneous heme crystallization and also enhanced Hz formation in reactions induced by whole regurgitates and lipids from regurgitates. Taken together these results indicate that hydrophobic environments are essential to promote heme crystallization and particularly in S.mansoni the LDPs plays a fundamental role in this process by allowing the hydrophobic association and crystallization of free heme in this parasite.