The efficacy of 2 strategies for control of bancroftian filariasis using mass diethylcarbamazine (DEC) chemotherapy was evaluated and compared in 2 endemic communities in Tanzania with pre-treatment microfilarial (mf) prevalences of 28.5% and 17.7%, and mf geometric mean intensities (GMI) of 588 mf/mL and 251 mf/mL, respectively. All individuals in the first community were offered DEC treatment with 6 mg/kg body weight given daily for 12 d (standard treatment). The second community was offered DEC treatment with 2 single doses of 6 mg/kg body weight given with an interval of 6 months (semi-annual single-dose treatment). Among those who were microfilaraemic before treatment, the mf clearance rates were 51.2% and 36.0%, and the mf GMIs were reduced by 98.6% and 92.2% one year after the start of the standard and the semi-annual regimens, respectively. At community level, the standard strategy and the semi-annual strategy reduced the mf prevalences to 15.1% and 11.6% (reductions of 47.0% and 34.5%) and the mf GMIs to 112 mf/mL and 102 mf/mL (reductions of 81.0% and 59.4%, respectively) one year after start of treatment. Both regimens resulted in remarkable improvements in small hydroceles among males presenting this condition before treatment. The lower efficacy of the semi-annual single-dose treatment in relation to the standard treatment in reducing microfilaraemias might be compensated for by continuing semi-annual treatments for a slightly longer period of time. Considering that the semi-annual treatment is easy to administer and more acceptable to the treated individuals, it may in the long run be a more feasible strategy for mass DEC chemotherapy than the standard treatment.