OBJECTIVE - To determine the possibility of an ethnic influence on the development of macrosomia (birth weight >90th percentile for gestational age) in gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS - We prospectively followed all African-American and Latino women enrolled in the Temple diabetes-in-pregnancy program. GDM was diagnosed in 103 African- American and 36 Latino women during the study period (1991-1994) according to the criteria of Carpenter and Coustan. All women were treated according to our previously published protocols. Data were collected on gestational weight gain, previous history of macrosoma, body mass index (BMI), and level of maternal glycemic control. RESULTS - Insulin therapy was required in 53 women (37.5%) to maintain fasting blood glucose levels at <95 mg/dl and 2-h postprandial levels at <120 mg/dl. Macrosoma developed in 50% of the neonates of Latino women versus 19% of neonates of African-American women (relative risk 2.68, 95% confidence interval 1.57-4.59). Potential confounding factors were not significantly different between the Latino and African-American women; mean blood glucose 96.6 ± 15.7 vs. 96.5 ± 22.4 mg/dl; BMI 29.0 ± 5.5 vs. 31.5 ± 8.2 kg/m2; pregnancy weight gain 29.2 ± 12.7 vs. 30.9 ± 20.5 lb; and parity 1.8 ± 1.5 vs. 1.6 ± 1.4, respectively. CONCLUSIONS - We have demonstrated that Latino women with GDM are at higher risk for having macrosomia infants in comparison with African-American women. This ethnic variation in fetal growth may be due to varying influences of in utero growth promoters among these populations as well as underlying genetic factors.