Biochemical alterations in the connective tissue matrix are a common feature of many diseases, and they account in major part for their functional impairment. Such alterations are especially important in acute and chronic inflammatory diseases where they may take the form of degradation of matrix components or their excessive accumulation leading to fibrosis. Although a wealth of morphologic information is available, very little is known about these changes at the biochemical level. Using human gingival tissue as a model, we have carried out studies aimed at assessing the effects of chronic inflammation on the collagen isotypes comprising the connective tissue matrix. Tissue obtained from patients undergoing surgical treatment for periodontitis was separated on the basis of clinical features into healthy and inflamed portions. After confirming the inflammatory status of each specimen histologically, each set of tissue pairs was extracted at 4 degrees C in 0.5 M acetic acid containing 1 mg/ml of pepsin, and the extracted collagens were fractionated with NaCl. Alpha chains were separated by polyacrylamide slab gel electrophoresis, and methods devised for their quantitation. The results showed that the proportions of type I and III collagens present in normal and inflamed tissues did not differ significantly. In contrast, the type V collagen, which accounted for 0.1 to 1.3% of the total collagens present in normal tissue, was increased by 2- to 9-fold in the chronically inflamed tissue. Because of the unique binding and connecting role type V collagen is thought to play, this alteration may have major pathologic and functional significance.