Summary Our objective was to investigate the factors that control chondrocyte division, namely, (1) steric hindrance caused by the surrounding matrix, (2) growth factors and (3) cell shape. Bovine articular cartilage explants and isolated chondrocytes were cultured in medium containing [ 3H]-TdR to measure DNA synthesis. The effect of enzyme treatment, growth factors and cell shape was investigated. Proteoglycan (PG) depletion did not stimulate DNA synthesis whilst disruption of the collagen architecture promoted incorporation of [ 3H]-TdR into DNA. DNA synthesis was also stimulated by IGF-1 in flattened chondrocytes but not in rounded cells. It was found that the control of chondrocyte division depends on several variably related factors that may act singly or together to induce cell division and that PG depletion alone is insufficient to induce DNA synthesis, but division was noted when PG depletion was secompanied by matrix disruption and cell shape changes. Cell shape appears to alter the chondrocytes ability to respond to IGF-1 as a mitogen.