Childhood disintegrative disorder is a neuropsychiatric syndrome characterized by normal development of verbal and nonverbal communication skills, social interaction, play, bladder and bowel control and motor behavior at least in the first two years, followed by regression between 2-10 years of age in two or more of the abovementioned developmental areas. Childhood disintegrative disorder is accepted to be very rare and the exact nature is still unknown. The cases of childhood disintegrative disorder mimic various disorders, especially at initial stages may confuse clinicians to diagnose. Ttherefore presentation of further clinical cases will assist clinicians to manage in the characterization of the disorder in different settings. Studies related to childhood disintegrative disorder are rare in literature. The purpose of this paper is to present the pharmacological intervention of two cases of childhood disintegrative disorder with risperidone. The first case was characterized by an onset of irritability, defiance and hyperactivity at age of four years, later followed by regression in language, bowel and bladder control and social interaction skills. The second case was a child in which the disorder started with regression in language as well as behavior disturbance at four years two months of age, and then language regression, poor bowel and bladder control and decline in social interaction skills were noticed. Risperidone was used as a pharmacological agent in both cases to control behavioral problems and benefit was achieved.