The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125l]dUrd-labelled tumor cells into B16 melanomabearing mice. Experiments were performed with mice undergoing acute or chronic reactions to bacterial endotoxin or zymosan, both of which were shown to modify the activity of the reticuloendothelial system as assessed by carbon clearance assays. On the one hand, the release of arrested melanoma cells from the lungs was retarded in mice with both endotoxin-and zymosan- induced acute inflammation. There was a parallel increase in the numbers of pulmonary tumor nodules which developed after injection of non-radiolabelled melanoma cells into similarly treated groups of mice. On the other hand, fewer tumor cells were retained in the lungs of mice undergoing chronic responses to endotoxin, and fewer pulmonary tumor nodules subsequently arose after injection of unlabelled cells. However, in mice pre-treated with zymosan, retention of melanoma cells was not different from that in controls and greatly increased numbers of pulmonary nodules grew in zymosan pre-treated mice receiving non-radiolabelled cells. These experiments were discussed in terms of the contribution of the reticuloendothelial system to the release of arrested cancer cells from the pulmonary vasculature.