The efficacy of two formulations of a topically applied 65% permethrin spot-on for dogs (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp.) was evaluated against experimental infestations of the cat flea, Ctenocephalides felis, and the brown dog tick, Rhipicephalus sanguineus. Thirty dogs were randomly allocated to treatment with 65 % permethrin in diethylene glycol monomethyl ether (original formulation), 65 % permethrin in propylene glycol monomethyl ether (test formulation), or to an untreated control group. Dogs assigned to treatment with a permethrin formulation received either 1 or 2 ml of the formulation in accordance with label directions on Day 0. One hundred unfed, adult cat fleas and 50 unfed, adult ticks were placed on each dog on Days -1, 5, 12, 19, 26, 33, and 40. Live fleas and ticks were counted on each dog on Days 2, 7, 14, 21, 28, 35, and 42. Treatment of dogs with either formulation of 65 % permethrin significantly (P <.05) reduced the number of live fleas and ticks from Days 2 through 42. No statistical differences were noted between the formulations regarding efficacy against C. felis or R. sanguineus.