A polypentapeptide (PPP) of tropoelastin having a repeating amino acid sequence of (Val-Pro-Gly-Val-Gly)n was evaluated for its potential to initiate in vivo calcification and to enhance bone formation in nonhealing calvarial wounds (8.0 mm) in 396 adult Walter Reed rats. There were four configurations of the PPP (molecular weight range of 50-100K dalton) consisting of 1-dry PPP; 2-coacervate PPP; 3-gamma irradiated, cross-linked PPP; 4-calcified, gamma irradiated, cross-linked PPP. These four iterations plus a control group of animals constituted the five treatment classes that were evaluated at days 1, 3, 7, 21, 42, and 147. Seventy two rats were used for each treatment and 36 rats for the control. Following euthanatization, specimens were placed into 70% ethanol, embedded in polymethyl methacrylate, sectioned at 3.5 micrometers, and alternating sections were stained with Masson-Goldner trichrome and von Kossa stains. Histomorphometric analysis was accomplished using a Zeiss Universal microscope (250 X) and Videoplan Image Analysis System to evaluate five random histologic fields from margin to margin of the craniotomy. Trabecular bony volume and area of calcification islands were quantitated. A Student's t test for unpaired data to determine treatment differences (within the same temporal groups) revealed that there was no significant difference between treatments and control for trabecular bony volume; however, there was a significant difference between experimentals and control for calcification islands (P less than 0.05) such that calcifications islands for the experimentals were greater than the control. There was not a significant difference between experimental treatments.(ABSTRACT TRUNCATED AT 250 WORDS)