To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic schistosomiasis, the study described in the present report evaluated the effects of dexamethasone on several parameters which reflect disease severity and morbidity. Parasitological, immunological, and histological parameters were analyzed in animals treated from the first day of infection or after 35 days of infection. In both situations, dexamethasone had no effect on the parasite burden but altered the egg distribution in tissue, indicating that under the schedule used it did not interfere with the development of adult worms or oviposition. Treated mice showed a decrease in the number of eggs in hepatic tissue, reduced granuloma sizes, reduced levels of granuloma maturation, and reduced collagen contents. Dexamethasone-treated mice also had decreased gamma interferon, interleukin-12 (IL-12), and IL-4 levels in serum and increased IL-10 levels in serum. Taken together, these data suggested a decrease in the severity of murine schistosomiasis and point to dexamethasone as a convenient and promising coadjuvant agent in the therapy of this infection.