Cystatins are physiological inhibitors of cysteine proteinases and they are widely distributed in human tissues and body fluids including saliva. We previously reported an increased cystatin activity in whole saliva of gingivitis and periodontitis subjects. Based on this result we decided to investigate the type and origin of cystatins involved in this increased cystatin activity by collecting both whole and parotid saliva of 25 healthy and 30 periodontitis subjects. Saliva samples were quantified for cystatins S and C by enzyme‐linked immunosorbent assay and cystatin activities were measured toward papain. Besides, three other salivary proteins were determined: the plasma protein albumin, the typical parotid derived amylase and the salivary immunoglobulin IgA. The present investigation shows that levels of total protein and cystatin activity as well as the levels of glandular derived proteins amylase and cystatin C were significantly higher in whole and parotid saliva of subjects with periodontitis than in healthy controls. Cystatin S, the major salivary cystatin. however was higher in the whole saliva of the healthy group. Whole saliva concentrations of albumin and IgA, originating from sources other than the glandular cells, were not different between healthy and periodontitis subjects and were also not correlated with the typical salivary gland proteins. In conclusion, this study provides additional evidence that the human salivary glands may respond to an inflammatory disease of the oral cavity, periodontitis, by enhanced synthesis of some acinar protein