Pruritus, or itch, is an unpleasant sensation that evokes a desire to scratch. Itch can be classified as either an acute or a chronic condition. Acute itch typically results from a bite or sting and can serve as a protective mechanism against tissue damage caused by parasites. However, chronic itch can result from the dysfunction of the immune and/or nervous systems. In mammals, pruritogens, or itch inducing agents, stimulate peripheral unmyelinated c-fiber pruriceptors, which are pruritogen detecting primary sensory neurons in the skin, causing transmission of sensory input to interneurons and projection neurons of the brainstem via the spinothalamic tract. This induces the itch sensation in the brain and the subsequent scratching behavior. Itch is a primary symptom in patients with broad range of illnesses, including skin diseases and systemic and metabolic disorders like liver and kidney diseases, HIV/AIDS and brain cancer. It is also seen in psychiatric disorders such as anxiety, depression, schizophrenia and delusions of parasitosis, leading to self-injurious behavior. The current understanding of pruritus in systemic diseases is limited due to the lack of sufficient animal models that mimic clinical chronic itch conditions. Furthermore, the antihistamines that are currently available for treatment of itch are typically ineffective in treating most cases of pruritus. Drosophila possess the homologs of many of the genes known to be involved in the mammalian pruritic pathway. Therefore, in current study, we are developing Drosophila as a model organism in order to investigate pruritus and identify key mediators of this condition in an established genetic model. To analyze the effects of pruritogens on Drosophila, we administer pruritogens to the fly and measure changes in their grooming behavior. Our preliminary results indicate that Histamine and Compound 48/80, which induces the natural release of histamine, both evoke longer grooming bout duration, compared to the control flies. Interestingly, two other pruritic mediators, Chloroquine and cowhage, do not have a significant effect on the flies’ grooming behavior, leading us to believe that Histamine and Compound 48/80 evoked a pruritic response. Histamine is one of the best studied pruritogens in mammals and Drosophila are known to have two Histamine receptors, Histamine-Gated chloride channel 1 (HisCl1) and Ora transientless (Ort). Both receptors have been studied for their role in photoreception and visual transduction, however, additional functions of these receptors have not been investigated. Therefore, we also set out to identify the receptor(s) responsible for the change in grooming behavior we observed, using Histamine receptor mutants. Based on our findings, we conclude that Drosophila can indeed be used as a model organism for investigating pruritus.