Systemic administration of Ad5 vectors capsid-displaying retro-DAF complement inhibitor significantly reduces Ad-mediated cytokine and chemokine release in C57BL/6 mice. C57BL/6 wild-type (WT) and C3-KO mice were intravenously injected with 0.75 × 10¹¹ vp/mouse (medium dose) or 2 × 10¹¹ vp/mouse (high dose) of Ad5-based control and experimental vectors. Plasma samples, collected at 6 hours after injection (n = 6 for virus-treated groups, N = 4 for Mock-injected groups) were analyzed with the use of a multiplexed bead array–based quantitative system. Statistical analysis was completed with the use of 1-way analysis of variance with a Student-Newman-Keuls post hoc test. The bars represent mean ± SD; plasma cytokine values that are statistically different from those in Mock-injected animals of both genotypes, *P < .05, **P < .01; statistically different values from WT_Ad5-GFP mice, #P < .05, ##P < .01. IL-12p40 indicates p40 subunit of interleukin-12; GCSF indicates granulocyte colony-stimulating factor; RANTES, regulated on activation normal T cell expressed and secreted; and MIP-1β, macrophage-inflammatory protein 1β.