Persistently elevated behavioural inhibition (BI) in children confers increased risk for anxiety disorders. However, little research has jointly examined exogenous and endogenous factors that may moderate BI stability in early childhood. To explore whether parent (i.e., parental overinvolvement, parent anxiety) and child (i.e., 5-HTTLPR and BDNF val66met genotype, positive emotionality) factors influenced the stability of early BI, a community sample of 371 preschoolers and their caregivers completed observational measures of child temperament, observational and questionnaire measures of parenting, and parent interviews for anxiety disorder history. Child BI at age 3 interacted with children’s 5-HTTLPR variants to predict age 5 BI; children with at least one copy of the short allele exhibited less stability of BI, indexed via associations between age 3 and age 5 BI. Findings are consistent with previous work indicating the 5-HTTLPR short variant increases plasticity to contextual influences, thereby serving to decrease BI stability in early childhood