Studies of collagen biosynthesis and prolidase activity were performed on cultured skin fibroblasts obtained from a female patient and her father, who displayed variable phenotypes of mild osteogenesis imperfecta (OI). For comparison, the same studies were also performed on age-matched controls. Biosynthesis of collagen in fibroblasts of the less affected father was reduced to approximately 50% of control levels, whereas in cells of the more severely affected daughter, it was decreased to about 20% of control levels. Furthermore, the decrease in collagen synthesis in OI fibroblasts was accompanied by a parallel decrease in prolidase activity and expression of beta1 integrin and insulin-like growth factor-I (IGF-I) receptors recovered from the cells. Therefore, prolidase, as well as IGF-I and beta1 integrin receptors involved in collagen metabolism regulation, may represent important factors influencing OI phenotype.