The pathogenetic mechanism of vasculitis in systemic lupus erythematosus (SLE) remains a subject of debate. Evidence for a direct pathogenetic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Supernatant concentrations of interleukin-1 beta and interleukin-6, and mRNAs encoding for interleukin-1 alpha and interleukin-1 receptor-1 were determined in cultured human umbilical vein endothelial cells (HUVEC), incubated with control IgG (n = 18), anti-dsDNA (n = 18), or IgG from the same lupus patient depleted of anti-dsDNA by affinity chromatography (anti-dsDNA-dep-IgG). Compared with control IgG, there was a significant increase of supernatant interleukin-1 beta and interleukin-1 alpha mRNA in endothelial cells incubated with anti-dsDNA. The supernatant interleukin-1 beta and interleukin-6, and mRNAs encoding for interleukin-1 alpha and interleukin-1 receptor-1, were significantly elevated in endothelial cells incubated with anti-dsDNA, compared with those incubated with anti-dsDNA-dep-IgG. Pretreating HUVEC with native DNA before incubating with anti-dsDNA did not result in an additive effect. These in vitro studies suggest that anti-dsDNA plays an important pathogenetic role in inducing inflammatory injury of vascular endothelium in SLE.