Fluorescent serum antibody determinations were used to examine whether children with obsessive-compulsive disorder (OCD) or less pervasive obsessive-compulsive symptoms (OCS) would show evidence of caudate nucleus involvement. Recent studies of OCD have documented smaller caudate nucleus volumes in adults with childhood onset than in normal controls, but not smaller putamen volumes. Thirty-eight cases were recruited from an ongoing study of childhood neurodevelopmental disorders. Nineteen samples from clinical cases had existing or previously documented OCS and attention-deficit hyperactivity disorder (ADHD) with or without concomitant tics. Nineteen additional clinical controls with ADHD, but without tics or OCS, were identified. The sera from clinical cases showed antibodies directed against caudate [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.1], putamen (OR 3.0; 95% CI 1.5 to 5.8), or both (OR 2.9; 95% CI 1.58 to 5.7) at a rate significantly higher than that of clinical controls, providing evidence of basal ganglia involvement in OCS. These preliminary data do not support a differential effect against caudate compared to putamen for these children, but suggest a more generalized central nervous system response.