The effect of various concentrations of praziquantel at different time intervals post-treatment on the ultrastructure of Schistosoma margrebowiei using scanning and transmission electron microscopy has been examined. The major changes involved blebbing of the entire surface tegument of both sexes (although more marked in males) together with vacuolation of the basal membrane accompanied by the development of membraneous whorls. These effects were progressively more marked with increased concentration and time of exposure resulting in severe erosion of the tubercles and collapse of the sensory organelles. Exposure of the underlying tegumental tissue resulted and paralysis and contraction of the suckers and neck region was apparent. Disruption of the subtegumental musculature and the appearance of vacuolation and membraneous whorl formation were seen. The gastrodermis was similarly affected and the S4 cells of the vitelline gland showed protein disruption of the vitelline droplets. Host cells were seen adhering to the surface of the worms following drug treatment and the synergism between PZQ and the action of the hosts immune system has been discussed.