We studied the effect of treatment with diethylcarbamazine (DEC) on immune responses to parasite antigens in humans infected with Brugia malayi. In vitro lymphocyte proliferative responses to microfilarial antigens increased in patients who became amicrofilaremic after treatment with DEC. No changes in reactivity were observed in amicrofilaremic individuals who were given DEC or in a small number of patients who remained microfilaremic after treatment. Reactions to other antigens (PPD and SKSD) were not affected by drug treatment. Serum titers of antibodies to the sheath of B. malayi microfilariae did not significantly change during the period of observation. These findings indicate that DEC partially reverses the state of cellular unresponsiveness to parasite antigens associated with patient filarial infections.