Double‐stranded RNA (dsRNA) induces the vascular cell adhesion molecule VCAM‐1 to high levels of expression in human umbilical vein endothelial (HUVE) cells. Although VCAM‐1 is also induced by the cytokine interleukin 1β (IL‐1β), activation of the dsRNA‐activated protein kinase (PKR) occurs only in response to incubation with dsRNA but not with IL‐1β. Incubation of HUVE cells with the synthetic dsRNA, poly (I) · poly (C), activates PKR with increased autophosphorylation, increased phosphorylation of the translation factor eIF2α, and increased activation of the transcription factor NF‐кB. Promoter analysis in HUVE cells using a VCAM‐1 promoter linked to CAT reporter gene demonstrates that poly (I) · poly (C) responsiveness resides in the minimal VCAM‐1 promoter that contains two NF‐кB sites, and deletion of the NF‐кB sites eliminates basal and poly (I) · poly (C)‐induced CAT activity, supporting the importance of NF‐кB in the poly (I) · poly (C)‐mediated induction of VCAM‐1. In vitro studies using purified reagents demonstrate that PKR is capable of phosphorylating IкBα (the inhibitory subunit of NF‐кB) in a dsRNA‐dependent manner. This suggests that phosphorylation of IкBα by PKR could be an initial step in the activation of NF‐кB by dsRNA. NF‐кB is also activated by IL‐1β in HUVE cells, but this activation occurs without increased PKR autophosphorylation or eIF2α phosphorylation. Poly (I) · poly (C) induces VCAM‐1 mRNA levels that are dramatically higher and sustained longer than levels induced by IL‐1β. Although phosphorylation of eIF2α interferes with protein translation, sufficient VCAM‐1 mRNA translation occurs in response to poly (I) · poly (C) to yield VCAM‐1 protein levels that are similar to levels that are induced by IL‐1bT. This suggests that the higher, sustained VCAM‐1 mRNA levels that occur in response to incubation with poly (I) · poly (C) compensate for the partial translational block resulting from increased eIF2α phosphorylation. These studies indicate that transcrip‐tional and translational regulatory events that occur in response to activation of PKR by dsRNA are important in the regulation of VCAM‐1 gene expression in HUVE cells.