Cognitive and motor deficits have been proposed as markers of abnormal neurodevelopment in schizophrenia and have been associated with genetic liability. In a multicenter study involving 106 subjects, 56 with deficit schizophrenia and 50 with nondeficit schizophrenia, we tested the hypothesis that the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism is associated with cognitive and motor deficits either in schizophrenia as a whole or in its deficit subtype. The COMT Val(158)Met polymorphism shared 6.6% of the executive/attention dysfunction variance in patients with schizophrenia and 15.6% of the motor impairment variance in patients with deficit schizophrenia. These results support the hypothesis that the COMT Val(158)Met polymorphism influences executive functions in schizophrenia and the neuromotor performance in the deficit subtype only.