Cytotoxicity of peritoneal macrophages (pMs) and peritoneal natural killer (pNK) cells toward xenogenic tumor cells was studied in anemic, suckling rats. Dams were fed 6, 12, or 250 mg Fe/kg diet ad libitum throughout gestation and lactation. Pups were injected intraperitoneally with 10(5) plaque-forming units of virus. Four days later cytotoxicity of pMs and pNK cells against YAC-1 mouse lymphoma cells was measured. Body weight, hemoglobin, hematocrit, and viable cell yield of pups were significantly decreased with decreasing dietary iron. pM cytotoxicity was significantly impaired in anemic pups at pM-target-cell ratios of 10:1 and 30:1 at 4 and 16 h (P less than or equal to 0.03). pNK-cell cytotoxicity was significantly impaired in anemic pups at pNK-target-cell ratios of 10:1 and 50:1 at 16 h. Iron-deficient diet consumed by dams throughout gestation and lactation resulted in anemic offspring whose immunologic defense by pMs and pNK cells against xenogenic tumor cells was significantly reduced.