Tic disorders, obsessive-compulsive disorder (OCD), and related conditions are prevalent disorders affecting as many as 0.3-3 percent of the pediatric population. They are chronic, relapsing disorders that can be associated with marked impairment and disability. Although clinical care has improved over the past decade, a significant number of patients fail to respond adequately or experience intolerable side effects. The etiologies of these disorders are unknown. It has been hypothesized that susceptible individuals develop symptoms of these disorders as a result of post-infectious autoimmune processes. Infections with group A beta hemolytic streptococci (GABHS) are thought to initiate these processes. Swedo, Leonard and colleagues (1998) have proposed that this subgroup of tic disorder patients, identified by the acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) follows a unique clinical course. Although this hypothesis is strengthened by: (1) the presence of potentially crossreactive antineuronal antibodies in the sera of a minority of patients with tic disorders and/or OCD; (2) enlarged basal ganglia in PANDAS cases; and (3) the finding that plasma exchange and intravenous immunoglobulin treatment are effective in reducing symptoms in PANDAS cases, this conceptualization remains controversial. The aim of this revised study is to validate the diagnostic concept of PANDAS by performing a prospective longitudinal study. Further cross-sectional studies cannot resolve this issue. The use of a prospective longitudinal design should permit a close examination of the timing of symptom relapses relative to GABHS exposure. Other specific aims focus on longitudinal fluctuations of psychosocial stress, anti-neuronal antibody levels and basal ganglia volumes in an effort to understand the pathobiology of PANDAS. If specific factors are associated with acute relapse, then the nature of these factors should provide insight into the immunologic mechanisms involved. This knowledge may provide a basis for the rational design of therapeutic and preventative interventions. More generally, the knowledge gained should advance our models of disease pathogenesis and clarify the interaction between psychosocial stress and psychoneuroimmunological mechanisms. These insights may be relevant to our understanding of other diseases including AIDS.