A transplantable granulocytosis-inducing mammary adenocarcinoma of mice was used to provide evidence about the role of tumor-generated factors in granulopoiesis. The original tumor produced high levels of colony-stimulating factor (CSF) in culture as well as inhibitor to CSF. The tumor was passaged repeatedly, both in host mice and in culture, and eventually displayed a varying capacity to induce granulocytosis. Tumors that were associated with either the induction of extreme granulocytosis or near-normal granulocyte levels were selected and passaged intermittently in vivo and in culture. Two tumor lines were thus isolated: one, line C-4a, inducing granulocytosis, and the other, line 34-4H, failing to induce granulocytosis. Both lines grow at the same rate in host mice, but in culture, each displays a distinct morphology. Measurement of CSF and inhibitor produced by each line in culture showed that line 34-4H retained the capacity to produce CSF and inhibitor in spite of losing the ability to influence granulopoiesis in vivo. This suggests that the various factors shown to influence granulopoiesis in vitro may have little or no role as physiologic regulators in vivo.