The effects of a fish oil diet on the myelopoietic and immunological parameters of normal mice and of mice bearing metastatic Lewis lung carcinoma (LLC-C3) tumors were compared to the effects of a corn oil or a mixed-fat rodent chow diet. This was studied soon after tumor appearance, on Day 17, when immune suppression was mediated by prostaglandin E2 (PGE2)-producing suppressor cells, and late in tumor development, on Day 28 when immune suppression was associated with myelopoiesis and the appearance of bone marrow-derived suppressor cells whose activity was not dependent on PGE2. Feeding a fish oil diet from Days 10 to 17 of tumor growth partially restored splenic T-cell blastogenesis, reduced spleen cell secretion of PGE2, and alleviated splenic suppressor activity. When fed from Days 21 to 28 of tumor growth, a fish oil diet neither restored T-cell blastogenesis nor alleviated suppressor cell activity. The fish oil diet increased the frequency of myeloid progenitor cells in normal mice and in mice bearing small or large tumors. Concurrently, the fish oil diet stimulated the appearance of bone marrow-derived suppressor cells. When administered after the establishment of palpable primary tumors, a fish oil diet also increased the formation of pulmonary lung nodules. In contrast to the fish oil stimulation of myelopoiesis and the associated suppressor cells, feeding a corn oil diet to tumor-bearing mice during Days 21 to 28 after tumor implantation reduced myelopoiesis and the presence of the associated bone marrow suppressor cells. These data show that a fish oil diet can minimize the immune suppression in tumor bearers when suppression is mediated by PGE2-producing suppressor cells, but can also induce myelopoietic stimulation leading to the appearance of bone marrow-derived suppressor cells and increased tumor metastasis.