Collection of family history data is important when evaluating environmental and genetic risk factors associated with epidemiologic studies. The aims of this study were to determine the percent concordance between maternal interview responses for family history information and blood relative questionnaire responses, and assess the independent effects of maternal age, education, income, marital status, gravidity, and study group status (case or control) on the validity of family history information provided by maternal interview. The results of the research suggest blood relative birth defect and cancer diagnoses provided by study mothers should be viewed with caution. Sensitivity estimates of maternal responses for blood relative birth defect diagnoses were low for both case and control groups. In contrast, sensitivity estimates of maternal responses for blood relative cancer diagnoses were higher for case mothers than control mothers. No independent factors of maternal age, education, income, marital status, gravidity, and study group status on the sensitivity of maternal telephone interview responses were found to be associated with sensitivity for blood relative birth defect diagnoses. For blood relative cancer diagnoses, analyses suggest that study group status was a significant factor in the determination of sensitivity with control mother reports being less accurate than case mother reports. Results of this study will be used to establish subject recruitment protocol and to design the family history questionnaire for an upcoming multi-state genetic epidemiologic case-control investigation of facial clefts.