This study was designed to investigate the effects of substances released from non-injured and injured bovine arterial endothelial cells on 125I-low density lipoprotein uptake and degradation by smooth muscle cells in culture. It was demonstrated that endothelial cell-released non-dialysable (molecular weight cut off 12-14000) substances significantly stimulated 125I-low density lipoprotein uptake and degradation by smooth muscle cells. Endothelial cell-released dialysable substances and endothelin-1 did not cause this stimulation. The increase in 125I-low density lipoprotein uptake and degradation by smooth muscle cells could be dissociated from cell proliferation. However, in endothelial cell-smooth muscle cell co-culture 125I-low density lipoprotein uptake and degradation by smooth muscle cells were not stimulated. Injury to endothelial cells by lipid-soluble smoke particles or ultraviolet light, which reduced total cellular protein by 15-25%, enhanced the endothelial cell release of the substances stimulating 125I-low density lipoprotein uptake. The results are discussed in relation to atherogenesis.