Sixteen controlled laboratory studies, involving 420 kittens and cats, were conducted to evaluate the efficacy and safety of topically applied formulations of imidacloprid and moxidectin for the prevention of feline heartworm disease, treatment of flea infestations and treatment and control of intestinal nematodes. Unit-dose applicators and the dosing schedule used in these studies were designed to provide a minimum of 10mg imidacloprid and 1mg moxidectin/kg. Treatments were applied topically by parting the hair at the base of the skull and applying the solution on the skin. Imidacloprid treatment alone did not display activity against Dirofilaria immitis or intestinal nematodes and moxidectin treatment alone provided little or no activity against adult Ctenocephalides felis infestations. The formulation containing 10% imidacloprid and 1% moxidectin was 100% efficacious against the development of adult D. immitis infections when cats were treated 30 days after inoculation with third-stage larvae. A single treatment with this formulation also provided 88.4-100% control of adult C. felis for 35 days. Imidacloprid/moxidectin was 100% efficacious against adult Toxocara cati and 91.0-98.3% efficacious against immature adults and fourth-stage T. cati larvae. The formulation provided 98.8-100% efficacy against adult Ancylostoma and immature adults and third-stage A. tubaeforme larvae. Monthly topical application with 10% imidacloprid/1% moxidectin is convenient, efficacious and safe for the prevention of feline heartworm disease, treatment of flea infestation and for the treatment and control of intestinal nematode infections of cats.