Studies on neural and behavioral correlates of the serotonin transporter gene polymorphism (5-HTTLPR) strongly suggested interaction effects between the 5-HTTLPR genotype and environmental conditions on infant emotionality development. However, empirical studies that involve human infants are rare. The present study thus analyzed the interaction of the 5-HTTLPR genotype with the quality of maternal parenting behavior on the development of negative emotionality and fear in infancy. In a sample of 69 healthy firstborn infants, negative emotionality and fear were assessed at 4, 8, and 12 months using a multi-method approach. The quality of previous parenting has been operationalized as the quality of the mother–infant attachment relationship measured by the strange situation procedure at 18 months. Corresponding to hypotheses, to their caregiver insecurely attached infants who were homozygous for the s-variant of the 5-HTTLPR genotype developed a high level of negative emotionality and fear. The results thus are in line with the experimental results in the non-human primate model and point to a more pronounced susceptibility of s/s carrying infants to early rearing experiences.