The study aimed to determine whether a consistent dose-response association can be demonstrated, after adjustment for maternal age and White classification, between glycosylated hemoglobin (HbA1c) values before conception and in the first trimester of pregnancy of insulin-dependent diabetic mothers and adverse fetal outcome (abortions and major malformations). This is a historical follow-up study based on medical records in a geographically defined catchment area. The study comprised 60 pregnancies with HbA1c determinations before pregnancy and 161 with HbA1c in the first trimester in women with type 1 diabetes admitted between 1980 and 1992. Relative risk calculations indicated a highly significant and consistent correlation between HbA1c values above 6.6% and adverse fetal outcome after adjustment for differences in maternal age and White classification. Our data support a clinically significant and consistent relationship between adverse fetal outcome and HbA1c in the first trimester of pregnancy of type 1 mothers, without any indication of a cut-off level below which further improvement in HbA1c was of minor importance.