The migration of Schistosoma mansoni cercariae and schistosomules, and the cellular responses of the hosts to these parasites, in primary and challenge infections, were examined and cine-recorded in vivo in the hypodermal tissues in Algire chambers which had been inserted in dorsal skins of C3H/HeJ mice and cheek pouches of Syrian hamsters, and checked in serial sections. In hamsters, many cercariae penetrated blood vessels within minutes after being injected into their chambers, in contrast to mice, in which penetration into vessels was scanty during the first hour. Schistosomule penetration into blood vessels was slow in both species. To ascertain whether or not the cercariae that had rapidly penetrated blood vessels in hamsters were capable of producing the disease, the chambers were removed a few hours after infection had been induced. Eight to 10 weeks later it was found that the parasites had produced the disease, since egg granulomas were found in the liver of hamsters. The cellular reactions of the hosts to the parasites revealed that granulocytes adhered first and most extensively to the tails of cercariae in essentially equal amounts in primary and challenge infections, but the adherence of such cells to the body of cercariae was geater in challenge infections. Nevertheless, an appreciable number of cercariae in both naive and challenge-infected animals were free of granulocytes or had less than five cells adhering to them. Furthermore, granulocyte adherence to cercariae or schistosomules was not necessarily permanent; the latter were usually free of cells a few hours after infection had been induced. Another difference between naive and challenge infections was that cercarial motility was more rapidly depressed in the latter infections.