Abstract Nitric oxide (NO⋅) can induce transient [Ca2+] changes in endothelial cells not different from receptor mediated signalling. Whether this Ca2+ signal may provide a link with IL-8 secretion induced by NO⋅ donors was investigated in human endothelial cells. Sodium nitroprusside (SNP) and S-nitroso-N-acetyl-dl-penicillamine (SNAP) dose dependently increased IL-8 production in this cell type. Additive IL-8 secretion was found with TNFα. Buffering intracellular Ca2+ with MAPT/AM suppressed NO⋅ induced [Ca2+]i changes and reduced subsequent IL-8 secretion. The additive effect of both NO⋅ donors on TNFα induced IL-8 secretion was completely blocked in the presence of MAPT/AM. SKF 96365, which has been shown to block receptor mediated Ca2+ entry, and TMB-8, which blocks intracellular Ca2+ release, both inhibited IL-8 secretion, particularly when TNFα was used as a costimulator, indicating that [Ca2+]i changes are important components of IL-8 induction by NO⋅.