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OBJECTIVE: This study was designed to investigate the link among attention deficit hyperactivity disorder (ADHD) in adults, novelty-seeking temperament, and the 48-base pair (bp) dopamine D4 receptor (DRD4) gene variant. METHOD: This study drew from a larger molecular genetic study of ADHD in which the ascertainment criterion was having an affected sibling pair with ADHD. Parents (N=171) from 96 families provided data. Of the 171 parents, 56 (33%) had a lifetime history of ADHD, with 28 (50%) continuing to meet DSM-IV criteria (i.e., “persistent” ADHD). Latent variable modeling was used to test whether the DRD4 gene variant or Temperament and Character Inventory factors could predict ADHD. RESULTS: Using latent variable modeling, the authors were able to confirm the first-order factor structure of the Temperament and Character Inventory. Furthermore, novelty seeking predicted ADHD lifetime diagnosis (R2=26%), while the DRD4 gene variant independently predicted ADHD (R2=5%) but not novelty seeking. CONCLUSIONS: In this unique sample of parents from multiply affected ADHD families, novelty seeking and the 48-bp DRD4 variant were associated with a lifetime history of ADHD. However, the association between novelty seeking and ADHD does not appear to be due to variation in the 48-bp DRD4 variant.