The serum concentrations of collagen type IV,7S, collagen type IV,nc1, and aminoterminal type III procollagen peptide immunoreactive components were measured by means of specific radioimmunoassays during development of granulation tissue in rats. The results were compared with tissue deposition of basement membranes and interstitial collagens in the granulation as measured morphometrically. A parallel sequential pattern in tissue deposition of collagen types III and IV, and serum increase of collagen types III- and IV-related fragments, was observed. Serum collagen type IV was less sensitive as a marker for development of granulation tissue than the serum procollagen type III N-peptide. This was in accordance with a low collagen type IV/interstitial collagen ratio in the granulation tissue. However, a cross-sectional study showed that serum collagens types IV,7S and IV,nc1 may be useful as early quantitative indicators of granulation tissue formation. Simultaneously, measurement of collagen type IV- and procollagen type III N-peptide-related antigens in serum provides a differentiated reflection of the dynamic matrix processes in developing granulation tissue.