Arachidonic acid metabolism was examined in a series of strongly malignant murine fibrosarcoma cell lines and in a series of weakly malignant lines isolated from the same tumors. The cells were examined in the unstimulated state and after stimulation with 12-O-tetradecanoyl phorbol acetate (TPA), laminin or fibronectin. All 3 agents were known from previous studies to induce adherence and motility in the murine fibrosarcoma cells. When the cells were prelabelled with 3H-arachidonic acid, all 3 agents stimulated the release of radioactivity into the supernatant fluids. The response to TPA was rapid while the response was slower but sustained when either laminin or fibronectin was used as the stimulating agent. This is of interest because TPA induces a rapid but transient adherence response in the same cells while laminin and fibronectin induce a slow, sustained response. Examination by radioimmunoassay procedures indicated that both control cells and stimulated cells were able to produce a variety of lipoxygenase and cyclooxygenase metabolites. In quantitative terms, the strongly malignant cells were more active than their weakly malignant counterparts. They released greater amounts of radioactivity into the supernatant fluid and produced a greater quantity of arachidonic acid metabolites, particularly prostaglandin E2, than did the corresponding weakly malignant cells. This is of interest because previous studies have shown that while both the strongly and weakly malignant cells respond in the adherence assay to TPA, laminin and fibronectin, only the strongly malignant cells demonstrate directional motility (chemotaxis and haptotaxis).