The objective of the present study was to assess the effect of terbinafine treatment in hamsters infected with Leishmania chagasi. Four of five groups of hamsters were infected with 3 x 10(7) L. chagasi promastigotes by the intracardiac route and submitted to different treatments of 30 days duration starting on the 30th day after inoculation. Group 1 was treated with 100mg/kg terbinafine PO, group 2 was treated with 80 mg/kg Glucantime IM, and group 3 was treated with a combination of the same dose of each drug by the same routes. Group 4 (control) received vehicle (Tween 80 [0.1%]+CMC[0.5%]+H(2)O [0.5 ml], PO). Spleen parasite burden and spleen relative weight were determined 3 days after the end of the treatment. The results were analyzed by the Kruskal-Wallis test (P < 0.05). There was no difference between the infected untreated and terbinafine-treated groups in spleen parasite burden (15.81+/-15.81 vs. 13.00+/-12.94, respectively). Terbinafine plus Glucantime (6.11+/-5.90) and Glucantime alone (4.83+/-4.82) significantly reduced spleen parasite burden compared to the infected untreated group (15.81+/-15.81, P<0.01). There was a difference in the relative weight of the spleen between the naïve and the infected untreated groups (2.5+/-0.2 vs. 9.8+/-1.0, respectively) as well as between the naïve and terbinafine groups (2.5+/-0.2 vs. 10.0+/-1.4, respectively). Glucantime alone and Glucantime plus terbinafine (2.5+/-0.2 and 4.2+/-0.6) significantly reduced the weight of the spleen in comparison with the infected untreated group. Even so, the spleen parasite burden was directly related to spleen weight. Terbinafine alone at the dose and schedule used had no effect on spleen parasite burden or relative spleen weight of L. chagasi-infected hamsters.