In New Zealand white rabbits bearing the transplantable VX2 carcinoma intramuscularly in the hind limbs uniformly a granulocytosis syndrome developed, characterized by peripheral blood neutrophilia and marked granulocytic bone marrow hyperplasia, whereas the syndrome did not always develop in animals bearing the tumor intraabdominally. The relationship between the extent of pulmonary metastases and granulocytosis/bone marrow hyperplasia was significant (P less than 0.005). This positive correlation (correlation coefficient = 0.85) existed for both animals bearing intraabdominal tumors and animals bearing intramuscular tumors. The granulocytic syndrome occasionally occurred in rabbits with mild degrees of pulmonary metastatic involvement, but never with total absence of pulmonary metastases. Hypercalcemia occurred prior to the appearance of pulmonary metastases and was not essential to the development of granulocytosis. These data suggest that granulocytosis in VX2 carcinoma-bearing rabbits is dependent on the presence of tumor in the lungs and is not directly related to implantation site. This tumor-bearing animal model may be suitable for studies of tumor-associated granulocytosis in vivo.