Experimental inflammation induced in cultured chondrocytes by inflammatory cytokine IL-1 beta stimulates collagen degradation by metalloproteinases. We propose that nitric oxide (NO) may represent down stream signaling molecule of IL-1-induced collagen degradation in chondrocytes. It was found that IL-1 beta induced the activity of MMP-2 and MMP-9 during the 48 h time course of the experiment, especially after 24h incubation, while DETA/NO, donor of NO, stimulated the process at 12h incubation. The mechanism of IL-1-dependent stimulation of NO production was found at the level of iNOS expression and activation of NF-kappaB. We found that hyaluronic acid (HA) counteracted IL-induced degradation of collagen in chondrocytes. Although, HA by itself had no effect on the metaloproteinases activity, when added to IL-1 beta or DETA/NO treated chondrocytes it contributed to the restoration of the MMPs activity to the control level. The mechanism of this phenomenon involves inhibition of NF-kappaB activation. The data suggest that NO may represent a target molecule for protective effect of hyaluronic acid on interleukin-1-induced stimulation of metaloproteinases activity in cultured human chondrocytes.