In a comparative study, the influence of several polypeptide growth factors on proliferation and matrix synthesis in secondary mandibular condylar and primary costal cartilage of the rat were determined using a serum-free culture system. Somatomedin-C, multiplication-stimulating activity (MSA), epidermal growth factor (EGF) and insulin had a significant dose-dependent stimulating effect on proliferation in mandibular condylar cartilage. In costal cartilage, the same factors as well as parathyroid hormone (fragment 1-34), platelet-derived growth factor (PDGF) and high doses of human growth hormone (1 microgram/ml) significantly stimulated proliferation. Matrix synthesis in both cartilages could only be stimulated by high doses of insulin (100 micrograms/ml) and in costal cartilage also by parathyroid hormone. In this culture system fibroblast growth factor reduced proliferation and matrix production, while cartilage-derived factor had no marked effect on the growth processes in both cartilage types. Prominent differences between condylar and costal cartilage were demonstrated by the effects of parathyroid hormone and fetal calf serum. Although the effects on matrix synthesis were very moderate in the tissue culture system used, this study demonstrates that most factors conducive to growth in primary cartilage also stimulate growth in condylar cartilage only exposure to growth substances that interfere with the differentiation of prechondroblasts into chondroblasts, a process that is specific for appositionally growing secondary cartilage, may result in different responses between primary and secondary cartilage.