Among important unsolved problems relating to the biology of schistosomes in definitive and intermediate hosts are: classification of post-cercarial growth stages, elucidation of the migration route of young worms in definitive hosts, and reaction of intermediate and final hosts toward a new infection. Schistosomatium douthitti was used for the study of the above problems for it is endemic in small mammals and snails in Michigan. Mice, Peromyscus maniculatus and Mus musculus, were used as definitive hosts. Snails, Lymnaea stagnalis appressa, were used as intermediate hosts. Both kinds of hosts were suitable for these experiments. Post-cercarial development of each sex is divided into nine stages, based on development of the genital system which is traced from the twelve cell stage to sexual maturity. This classification is more consistent and easier to follow than classifications based on other criteria employed for other schistosomes. Because of variation in rate of migration and location, worms of the same age may present unequally developed genital systems. Seven day worms have doubled their length; eight day females are narrower than males; ten day worms are apparently sexually dimorphic, and twelve day worms are sexually mature. Before eight days, the ventral sucker is smaller than the oral, reaching the same diameter on the eighth day, and is larger thereafter. Intestinal ceca unite in old worms and occasionally in young. Eyespots are sometimes present in young sexually mature worms. Laurer’s canal is first reported for S. douthitti. The route of migration in the final host was determined by experiments on 127 mice, four sectioned and others dissected at different ages of infection. Cercariae penetrate the intact skin, usually lie parallel to the skin surface, and do not feed on blood in the skin. They migrate through lymph vessels and nodes to the heart, and within pulmonary arteries to the lungs where they break through the arteries, wandering in the lung stroma and encysting briefly. Worms break through the surface of the lungs to the thoracic cavity, migrate to the liver through the diaphragm, along esophagus and postcaval vein, penetrate the surface of liver and enter the portal circulation. Beginning eight days after infection, males migrate to the mesenteric veins; females tend to stay in the liver; but the presence of males stimulates them to migrate to the intestinal veins. Some worms wander from the regular migration route, penetrating heart muscles, spinal cord, brain, thymus gland, thoracic lymph gland, kidneys and postcaval vein where they presumably die. The route of migration of S. douthitti from skin to heart corroborates results found by Koppisch (1937) for S. mansoni and the route from lungs to liver confirms the findings of Narabayashi (1915) for S. japonicum and of Lampe (1927) for mansoni. Prenatal infection was not observed. Younger snails are more susceptible than old to infection by miracidia, and snails exposed individually to single miracidia show a lower percentage of infection than snails of the same age exposed individually to several miracidia. Lack of bisexual infections in individually infected snails exposed later to miracidia is believed to be due to acquired immunity. The rare occurrence of bisexual infections in naturally or experimentally infected snails is explained by age immunity or immunity acquired by previous infection. In mice, partial immunity to reinfection probably occurs following establishment of worms.