Background: Isothiocyanates in cruciferous vegetables modulate signaling pathways critical to carcinogenesis, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of inflammation. Glutathione S-transferase (GST)M1 and GSTT1metabolize isothiocyanates; genetic variantsmay result in differences in biologic response. Objective: The objective of this study was to test whether consumption of cruciferous or cruciferous plus apiaceous vegetables altered serum concentrations of interleukin (IL)-6, IL-8, C-reactive protein (CRP), tumor necrosis factor (TNF) α, and soluble TNF receptor (sTNFR) I and II, and whether this response was GSTM1/GSTT1 genotype dependent. Methods: In a randomized crossover trial, healthymen (n = 32) andwomen (n = 31) aged 20-40 y consumed 4 14-d controlled diets: basal (vegetable-free), single-dose cruciferous (1xC) [7 g vegetables/kg body weight (BW)], double-dose cruciferous (2xC) (14 g/kg BW), and cruciferous plus apiaceous (carrot family) (1xC+A) vegetables (7 and 4 g/kg BW, respectively), with a 21-d washout period between each intervention. Urinary isothiocyanate excretion was also evaluated as a marker of systemic isothiocyanate exposure. Fasting morning blood and urine samples were collected on days 0 and 14 and analyzed. Results: IL-6 concentrations were significantly lower on day 14 of the 2xC and 1xC+A diets than with the basal diet [219% (95% CI:230%,20.1%) and220%(95%CI:231%, -0.7%), respectively]. IL-8 concentrationswere higher after the 1xC+Adiet (+16%; 95% CI: 4.2%, 35.2%) than after the basal diet. Therewere no effects of diet on CRP, TNF-α, or sTNFRI or II. Therewere significant differences between GSTM1-null/GSTT1+ individuals for several biomarkers in response to 1xC+A compared with basal diets (CRP:237.8%;95%CI:258.0%,27.4%; IL-6:248.6%;95%CI:249.6%,212.0%; IL-8: 16.3%;95%CI: 6.7%, 57.7%) and with the 2xCdiet comparedwith the basal diet (IL-8:233.2%;95%CI:243.0%,21.4%; sTNFRI:27.5%; 95%CI:212.7%,22.3%). Therewere no significant reductions in biomarker concentrations in response to diet amongGSTM1+/GSTT1+orGSTM1-null/GSTT1-null individuals. Twenty-four-hour urinary isothiocyanate excretionwas not associatedwith any of the inflammationmarkers overall; however, IL-6was inversely associatedwith total isothiocyanate excretion inGSTM1-null/GSTT1-null individuals (β =-0.12;95%CI:20.19,20.05). Conclusions: In this young, healthy population, consumption of cruciferous and apiaceous vegetables reduced circulating IL-6; however, results for other biomarkers of inflammation were not consistent.