The cercariae of Schistosoma mansoni become transformed into schistosomula during host skin penetration. We have found that large acidophilic compartments are detected in schistosomula but not in cercariae or in any other stages of the parasite by use of the fluorescent dye LysoTracker, a dye specific for mammalian lysosomes. Some of these large acidic compartments incorporated monodansylcadaverine, a specific dye for autophagosomes. We have used potent inhibitors (wortmannin and 3-methyladenine) and a potent inducer (starvation) of autophagy to show that the pathway to the formation of the acidic compartments requires specific molecular signals from the environment and from the genome. Certain doses of ultraviolet light inhibited significantly the formation of the acidic compartments, which may indicate disruption of the lysosome/autophagosome pathway. We have also defined two proteins that are commonly associated with lysosomes and autophagosomes in mammalian cells, the microtubule-associated membrane protein (MAP-LC3) and lysosome-associated membrane protein (LAMP-1), in extracts of schistosomula. We suggest that the autophagy pathway could be developed in transformed schistosomula.