Each medium renewal of confluent primary heart cell cultures derived from new born rats induces a pleiotypic response which leads to active proliferation. The presence of serum in the culture medium is essential for this activation of growth. Nutrient starvation prior to the activation decreases the response of the cells to serum. Serum starvation prior to the activation increases the serum dependence of the incorporation of labelled leucine but leaves the serum dependence of DNA synthesis unchanged. Ageing in culture decreases the serum dependence of the incorporation of labelled thymidine and amino acids but maintains it for alpha amino isobutyric acid transport. Several active components in human serum were distinguished by fractionated dialysis. A single dialyzable component stimulates both thymidine and amino acid incorporations. The transport of 2 deoxy-D-glucose is activated by another rapidly dialyzing component. The activation of alpha amino isobutyric acid transport may result from several components that are distanct from the previous ones. These results imply that a multiplicity of controls underly the pleiotypic activation of heart cell cultures by medium changes.