The intrinsic content of serotonin (5HT) and the uptake of 5HT by Schistosoma mansoni taken from mice which were given a single intramuscular therapeutic dose of hycanthone were studied. Drug-exposed worms were found to have intrinsic values of 5HT which were similar or slightly less than controls. Uptake measurements were made on single and on paired worms recovered from mesenteric, portal, or hepatic sites and incubated in 75% horse serum or in Fischer's medium. All groups of treated worms were found to take up, on average, similar or lower amounts of 5HT compared to controls. These findings are in contrast to a recent report of very considerable increases in content or in 5HT acquisition in vitro by hycanthone-exposed parasites. This communication suggests that the mode of action of hycanthone cannot be explained as being due to increased 5HT uptake. Morphological changes in hycanthone-treated worms include loss of body weight and size, loss of hemoglobin pigment from the gut, deterioration of the tegument, and derangement of the vitellaria. The loss of gut contents occurs early after exposure to hycanthone and may indicate that interference with gut physiology and the nutritional state of the worms is one consequence of the drug, although the mechanism of these changes has not yet been elucidated.