The authors used a longitudinal, prospective design to investigate a moderation effect in the association between a genetic vulnerability factor, a variable nucleotide repeat polymorphism in the promoter region of "5HTT" (5-HTTLPR), and increases in youths' substance use. The primary study hypothesis predicted that involved-supportive parenting would attenuate the link between the 5-HTTLPR polymorphism and longitudinal increases in substance use. African American youths residing in rural Georgia (N = 253, mean age = 11.5 years) provided 4 waves of data on their own substance use; the mothers of the youths provided data on their own parenting practices. Genetic data were obtained from youths via saliva samples. Latent growth curve modeling indicated that 5-HTTLPR status (presence of 1 or 2 copies of the s allele) was linked with increases in substance use over time; however, this association was greatly reduced when youths received high levels of involved-supportive parenting. This study demonstrates that parenting processes have the potential to ameliorate genetic risk. (Contains 2 tables, 1 figure and 1 footnote.)