Previous research has demonstrated that both sex and familial pain history can influence clinical pain, and sex is known to affect experimental pain responses. However, the potential interactive effects of sex and family history on pain-related symptoms and experimental pain have not been investigated. This experiment examined recent pain complaints and laboratory pain responses as a function of sex and reported family history of pain in 212 (122 female, 90 male) young adults. All subjects completed questionnaires regarding family history of pain, recent pain experiences, and psychological measures of hypervigilance. Then, warmth detection thresholds, heat pain thresholds and heat pain tolerances were determined. Results revealed sex-dependent influences of familial pain history on recent pain complaints and experimental pain responses. Specifically, a positive family history of pain was associated with increased reports of pain over the previous month and poorer general health as well as enhanced sensitivity to thermal stimuli among females but not males. Higher levels of hypervigilance accounted for some of the family history effects on recent pain complaints but not experimental pain measures. Potential mechanisms underlying these effects of family history among females are discussed.