Four bisbenzylisoquinoline alkaloids, antioquine, berbamine, gyrocarpine and isotetrandrine were tested in BALB/c mice infected with Leishmania amazonensis (IFLA/BR/67/PH8 or MHOM/GF/84/CAY‐H‐142) or L. venezuelensis (VE/74/PM‐H3). The treatments were initiated 1 day after the parasitic infection, with alkaloid at 100 mg/kg/day for 14 days and the reference compound, meglumine antimonate (GlucantimeR) at 200 mg/kg/day. Antioquine, berbamine and gyrocarpine were less potent than Glucantime against L. amazonensis (PH8). Only isotetrandrine exhibited activity approximately equal to or greater than Glucantime in BALB/c mice infected with L. amazonensis (PH8 or H‐142) and showed significant activity against L. venezuelensis. Experiments with a single local treatment on the footpad, 2 weeks after parasitic infection with L. amazonensis (PH8), showed that isotetrandrine at 200 mg/kg was less active than Glucantime at 400 mg/kg.