Objective This study examined the differences in the inflammatory cytokine interleukin (IL)-6 and the immunoinhibitory cytokine IL-10 in the amniotic fluid of black and white women in spontaneous preterm birth. Methods In this study, 321 amniotic fluids from cases (preterm birth 36 or fewer weeks’ gestation) and controls (normal term delivery longer than 37 weeks’ gestation) were collected (147 cases 49 blacks and 98 whites and 174 controls 85 blacks and 89 whites) at the time of active labor. IL-6 and IL-10 concentrations were measured by immunoassays. Using normal-term delivery as controls, logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for preterm birth. Results A significant difference in IL-6 concentration was observed in white cases (cases: 3773 pg/mL; controls: 1682 pg/mL; P = .0003), compared with controls, but not in blacks (cases: 2042 pg/mL; controls: 2366 pg/mL; P = .6). In a combined multivariable analysis, when the highest and the lowest quartiles of IL-6 were compared in whites, the ORs (95% CI) for preterm birth across quartiles were 1.74 (0.62-4.88), 1.09 (0.39-3.02), and 5.68 (2.15-15.0). No such association was found in blacks. IL-10 concentration was not different between cases and controls in either race. Conclusions Race-specific associations exist between IL-6 but not IL-10 concentration and preterm birth. Elevated IL-6 concentrations are associated with preterm birth in whites but not blacks.