AbstractSmooth pursuit eye movement (SPEM) deficit is an established schizophrenia endophenotype with a similar neurocognitive construct to working memory. Frontal eye field (FEF) neurons controlling SPEM maintain firing when visual sensory information is removed, and their firing rates directly correlate with SPEM velocity. We previously demonstrated a paradoxical association between a functional polymorphism of dopamine signaling (COMTgene) and SPEM. Recent evidence implicates the dopamine transporter gene (DAT1) in modulating cortical dopamine and associated neurocognitive functions. We hypothesized thatDAT110/10 genotype, which reduces dopamine transporter expression and increases extracellular dopamine, would affect SPEM. We examined the effects ofDAT1genotype on: Clinical diagnosis in the study sample (n = 418; 190 with schizophrenia), SPEM measures in a subgroup with completed oculomotor measures (n = 200; 87 schizophrenia), andDAT1gene expression in FEF tissue obtained from postmortem brain samples (n = 32; 16 schizophrenia).DAT1genotype was not associated with schizophrenia.DAT110/10 genotype was associated with better SPEM in healthy controls, intermediate SPEM in unaffected first‐degree relatives of schizophrenia subjects, and worse SPEM in schizophrenia subjects. In the gene expression study,DAT110/10 genotype was associated with significantly reducedDAT1mRNA transcript in FEF tissue from healthy control donors (P < 0.05), but higher expression in schizophrenia donors. Findings suggest regulatory effects of another gene(s) or etiological factor in schizophrenia, which modulateDAT1gene function. © 2008 Wiley‐Liss, Inc.