ABSTRACT A 10-week double-blind, placebo-controlled design was employed to investigate the effectiveness of clomipramine (CMI) versus placebo in 16 outpatients (ages 10-18 years) with obsessive-compulsive disorder (OCD). While a trend favoring clomipramine was observed, the difference in efficacy between clomipramine (N=8) and placebo (N=8) did not reach statistical significance, partly due to small sample size (N = 6,8). Post-hoc exclusion of two clomipramine-resistant subjects with subtle neurological impairments did, however, yield a statistically significant improvement with drug treatment. Neurological impairments are commonly seen in children with OCD, and may be a risk factor for the disorder during childhood. Speculatively, subtle neurological impairments may also predict resistance to CMI therapy in some patients, and influence the outcome of clinical and research medication trials, depending on differences in neurological inclusion and exclusion criteria.