The relationship between plasma levels of 15-keto-13, 14-dihydroprostaglandin E2 (15K-H2-PGE2) and serum calcium levels was studied in nontumor-bearing rabbits and in rabbits bearing the VX2 carcinoma intramuscularly and intra-abdominally. The plasma levels of 15K-H2-PGE2 in the two groups of tumor-bearing animals did not vary significantly but was several fold greater than in nontumor-bearing rabbits. Rabbits bearing the VS2 carcinoma intramuscularly developed hypercalcemia between the second and third week after implantation of neoplastic tissue and remained hypercalcemic until they expired. The serum calcium levels in rabbits bearing the VX2 carcinoma intra-abdominally did not vary significantly from those of nontumor-bearing rabbits. The differences in the serum calcium levels in rabbits bearing the VX2 carcinoma at intramuscular and intra-abdominal implant sites may be related to different extents of metabolism by the lung and by the liver of prostaglandin E2 or other cyclooxygense of polyenoic fatty acids produced by the tumor.