Three parameters have been identified that provide useful indices of longitudinal growth rate in rabbit epiphyseal plates. Specifically, we have examined the relationship between longitudinal growth rate and (1) growth-plate thickness; (2) the rate of cell division by proliferating chondrocytes; and (3) 35SO4 incorporation associated with matrix synthesis. There were statistically significant correlations between growth rate and each of the three experimentally determined parameters. Growth rate increased in direct proportion to growth-plate thickness, rate of chondrocyte proliferation, or 35SO4 incorporation associated with matrix synthesis. Of the three parameters, the rate of cell division of proliferative chondrocytes, as determined by counts of 3H thymidine-labeled cells following autoradiography, appeared to provide the most sensitive index of growth rate. However, used in combination, determination of the three parameters should make it possible to assess the relative contributions of changes in the numbers of cells, in the rate of chondrocyte proliferation, and in extracellular matrix synthesis to over-all growth rate. CLINICAL RELEVANCE: Methods are described and data are presented that should make it possible to design studies of the factors that regulate and control the longitudinal growth rate of epiphyseal cartilage growth plates. The experimental design of this work is applicable to the study of hormonal regulation of over-all growth rates and to determination of whether the effects of certain hormones are due to their effect on cell proliferation or matrix synthesis. Such studies should contribute to a better understanding of the control of growth in normal individuals and in patients with disease.