Since skin is the only route of entry of the parasite in schistosomiasis patients, intervention at the level of skin penetration should control the infection. Several compounds were screened for their ability to protect against cercarial penetration. Hinokitiol (β-thujaplicin) was found to have a significant cercaricidal effect in vitro, although there is no information on its cercaricidal mechanisms. To study the kinetics of morphological changes in Schistosoma mansoni associated with exposure to hinokitiol in vitro, cercariae were incubated in media containing hinokitiol at different concentrations and examined by transmission electron microscopy (TEM). TEM revealed that ultrastructural changes occurred by 15 minutes post exposure, at a concentration of 25 μg/ml. Degenerative changes involving both tegument and deeper parenchymal structures were progressive with duration of exposure at the concentration of 50 μg/ml. These structural changes may account for the inability of hinokitiol-treated cercariae to infect the host.