Spinosad is a novel mode of action insecticide and acaricide derived from a family of natural compounds produced from fermentation of the actinomycete, Saccharopolyspora spinosa. Although spinosad has been shown to have rapid knockdown and 1 month of residual efficacy against fleas (Ctenocephalides spp.) following oral administration in dogs, potential activity against ticks infesting dogs has not been determined. To address this possibility, a proof-of-concept laboratory efficacy study was conducted using dogs orally treated with spinosad and experimentally infested with the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae). In this randomized block (blocked by gender and pre-treatment tick counts), blinded, parallel-arm study, 12 dogs selected on health and ability to maintain pre-treatment tick populations were allocated equally among three groups: placebo-treated negative control, and spinosad in gelatin capsules at 50 and 100mg/kg administered per os. All treatments were administered once on Day 0. On days -6, -1, 7, 14, 21 and 28, each dog was infested with 50 unfed adult R. sanguineus, approximately 50% male and 50% female, obtained from the investigator's established tick colony. Tick comb counts were performed approximately 48 h post-infestation by study personnel who were blinded to treatments. Compared to geometric mean live tick counts in the control group, tick counts in the 50 and 100mg/kg spinosad doses were significantly (P<0.05) reduced by 94.8 and 97.2%, respectively, within 24h of treatment. Compared to geometric mean live tick counts in the control group at Days 9, 16, 23 and 30 after treatment, the 50mg/kg spinosad treatment group demonstrated 67.8, 49.1, 52.1 and 5.0% reductions, while the 100mg/kg spinosad treatment group demonstrated 88.6, 70.6, 61.9 and 71.3% reductions, respectively. This pilot efficacy study demonstrated that a single oral treatment with technical spinosad in gelatin capsules, at 50 and 100mg/kg, provides high efficacy against existing R. sanguineus infestations within 24h of dosing, and suggests that there is some post-treatment residual tick control in dogs for up to 1 month.