We determined whether the combination of the 48-bp variable number tandem repeat polymorphism of the dopamine (DRD4) gene and infants' (fussy-difficult) temperament predicted parenting sensitivity. The sample was comprised of 147 mothers and their 6-month olds. Sensitive parenting was assessed by coding filmed interactions between mothers and infants. Infant temperament was assessed by parents' reports on a standard questionnaire. Moderated regressions models, with maternal education and infants' interactive behavior as controls, were used to test our hypotheses. Results showed no main effects of either temperament or DRD4, though the maternal DRD4 x infant temperament interaction was significant. Probes indicated that parents with a DRD4 7-repeat allele behaved more sensitively to fussier infants and less sensitively to less fussy infants compared to parents without the 7-repeat allele. Among those parents, sensitivity did not vary with infant temperament. This pattern of results indicates that mothers are differentially susceptible to infant fussiness, dependent on the presence of the 7-repeat DRD4 allele.