Objective: To compare serum cytokine levels in patients with hyperemesis gravidarum with levels in healthy pregnant and nonpregnant women. Design: Case-control study. Setting: Clinical and academic research center. Patient(s): Thirty women with hyperemesis gravidarum, 30 healthy women in the first trimester of pregnancy, and 30 healthy nonpregnant women. Main Outcome Measure(s): Serum levels of interleukin-1beta, interleukin-2 receptor, interleukin-6, interleukin-8, and tumor necrosis factor (TNF)-alpha. Result(s): Median serum levels of interleukin-2 receptor and interleukin-8 did not differ significantly among the three groups. Serum levels of interleukin-1beta and interleukin-6 were significantly higher in healthy pregnant women than in healthy nonpregnant women. Median TNF-alpha levels were significantly higher in women with hyperemesis (25.8 pg/mL [range, 4.9-140 pg/mL]) than in healthy pregnant and nonpregnant women (10.85 pg/mL [range, 4.1-35.8 pg/mL] and 12 pg/mL [4.3-68.2 pg/mL], respectively). Conclusion(s): Levels of TNF-alpha were significantly higher in patients with hyperemesis gravidarum than in healthy pregnant and nonpregnant women. Thus, TNF-alpha may be involved in the etiology of hyperemesis gravidarum.