Comparative efficacy of mebendazole and flubendazole, a p−fluor analogue of mebendazole against the encysted larvae of Trichinella spiralis (USA strain) in the diaphragm of mice and rats were studied in order to provide a better understanding of the structure-activity relationship within the benzimidazole series. Drugs given 10–100 mg/kg/day for 3 consecutive days (35–37 days post-infection) or at 300 mg/kg, 35 days post infection were significantly effective in decreasing early encysted larvae in mice. No significant differences in effectiveness against the early encysted larvae could be observed between the drugs under the present experimental conditions. Mebendazole was found to be more effective that flubendazole in decreasing old encysted larvae in mice treated 70–72 days post-infection based on a comparative study of their ED50 values. When rats were given the drugs at the dose of 10 mg/kg/day for 3 consecutive days, mebendazole was significantly effective against both early and old encysted larvae while flubendazole was not.