It is well established that maternal multivitamin supplementation reduces the risk of neural tube defects and evidence suggests that it may be associated with other reproductive outcomes. The present study was prompted by a report from a randomized trial in Hungary which showed a 40% increase in multiple births among periconceptional vitamin users. Retrospectively collected data on multivitamin supplementation were obtained on multiple and singleton births from three separate studies: Atlanta Birth Defects Case-Control Study (ABDCCS) malformed and nonmalformed infants born 1968-1980, California Birth Defects Monitoring Program (CBDMP) malformed and nonmalformed infants born 1987-1989, and Boston University Slone Epidemiology Unit Birth Defects Study (SEU-BDS) malformed infants born 1987-1994. Supplementation was divided into three mutually exclusive categories based on timing: "periconceptional" use--before through at least the third month after conception; "early" use--beginning in the first month and continuing through at least the third month after conception; and "later" use--beginning in the second or third month after conception. For periconceptional use, four of five datasets showed a 30 to 60% greater prevalence of supplementation among mothers of multiple births. In contrast, this pattern was not evident for "early" and "later" use. Overall, the study findings are tentative, due to a lack of consistency across all five datasets and they should not alter recent recommendations related to folate supplementation for the prevention of neural tube defects.