The inflammatory response to microcrystals is one of the most powerful and intriguing examples of inflammation observable in man. Although many mechanisms of this reaction are well known, some aspects need to be further clarified, in particular those related to the self-limited nature of the process. Type and duration of the inflammatory reactions are mainly influenced by crystals characteristics, including shape and size, which, in turn may involve the crystal- binding of several proteins, essential for the modulation of cellular responses. Cells most involved in the acute attacks are macrophage and neutrophils, which are responsible for the secretion of several important mediators of inflammation, such as prostaglandins and cytokines. These substances may in turn influence both intensity and duration of the acute attack. The proinflammatory effects of interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha are counterbalanced by the anti-inflammatory activity of transforming growth factor (TGF)-beta, which may inhibit both the cell recruitment and cytokine synthesis. The role of TGF is crucial, not only by limiting acute inflammation but also by promoting formation and deposit of calcium crystals. However, the final effect of the balance between inflammatory and anti-inflammatory cytokines may also depend by other tissutal and cellular factors, not all of which are still completely understood.