The effects of low (5 mg/kg × 7) and high (20 or 30 mg/kg × 7) doses of cyclophosphamide on the formation an solubility of collagen in subcutaneous, porous implants, bones and incisional skin wounds were studied in young, male rats. At the 5 mg/kg schedule, effects from the drug were only detected as an increased solubility of collagen in implant connective tissue. At the 20 mg/kg schedule, there was a significant reduction of the synthesis and solubility of collagen in bones and in skin wounds. The 30 mg/kg schedule significantly depressed all the parameters studied except the specific activity of hydroxyproline in implants. Collagen stability seems to be impaired at low dose levels, whereas one of the main effects of high doses appears to be inhibition of collagen synthesis.