Stressexposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatalstress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatalstress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASDrisk. The present study examined a maternal genetic variation in the promoter region of the serotonintransporter gene (5-HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASDchildren recruited by the University of Missouri and Queen’s University were surveyed regarding the prenatal environment and genotyping on 5-HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5-HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposureto prenatalstress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternalgenotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatalstress.