A 10-year-old castrated male domestic cat was admitted to the hospital because of lifelong urine spraying of vertical surfaces. A diagnosis of territorial urine marking was made. Laboratory analytes for urine analysis, hemogram, serum biochemical analysis, and serum thyroxine concentration were within reference ranges, and testosterone concentration was consistent with the reference range of castrated male cats. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat's consistent use of the litter box. Cyproheptadine administration was recommended for at least 1 year before any attempt to withdraw its use. A follow-up phone call to the owner 8 months after the beginning of treatment revealed that the cat continued to have remission of inappropriate urination. Cyproheptadine, an antihistamine prescribed for its orexigenic effects in cats, has antiandrogenic effects in other species. Information in this report indicates that cyproheptadine is effective in the control of urine spraying even in castrated cats.