Lewis lung carcinoma cells (LLC) were isolated and cloned from metastatic lung nodules of C57BL/6 mice or from a cultured parental LLC line. Their dissemination abilities were defined in vivo by their capacities to disseminate to the lungs following s.c. or i.v. injection into mice and in an in vitro model for tumor dissemination by their ability to migrate out of glass capillary tubes. Cloned LLC cells with an enhanced dissemination capacity exhibited a rounded morphology, were nonadherent during in vitro culture, and readily migrated out of capillary tubes. In contrast, clones not capable of dissemination were adherent and spread during in vitro culture and did not migrate out of capillary tubes. Production of prostaglandin E2 by these clones was measured by a radioimmunoassay. An inverse relationship was observed between the extent of migration and dissemination of clones and their ability to secrete prostaglandin E2 in vitro and in vivo. However, the prostaglandin E2 did not regulate the migration-dissemination capacities of LLC clones as inhibiting prostaglandin synthesis did not alter their capacity to migrate in vitro or to lodge in the lungs following i.v. inoculation into mice.