Inflammation caused by insoluble microcrystalline calcium salts was compared with inflammation elicited by soluble carrageenan and monosodium urate crystals, in rats' paws. Local and systemic responses to four calcium crystals, viz. pyrophosphate, triphosphate, oxalate, and tartrate were studied. Changes in liver function, reflected in reduced serum albumin and increased sleep times in response to barbiturates, indicative of systemic inflammation, occurred despite the localized nature of the crystal induced inflammation. Serum thiol levels were also reduced. These altered functions were similar to, but less pronounced than, those accompanying the severe systemic inflammation produced by Freund's adjuvant. A copper glycine complex was effective in reducing foot swelling due to triphosphate, and edema due to oxalate. Colchicine had very little effect on the inflammation caused by the insoluble calcium salts but inhibited inflammation due to sodium urats crystals and soluble carrageenan. Crystal-induced inflammation that is outwardly localized may induce biochemical changes that are similar to changes found in systemic inflammation.