The intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) produces an environment conductive to primary plasmacytoma growth in as few as 3 days. After pristane injection, the total free peritoneal cell population increases from a normal value of 1.55 X 10(6) to 5.28 X 10(6) and remains at this elevated level for at least 50 days. The adherent peritoneal cell population, composed of both mononuclear cells and polymorphonuclear leukocytes, is the primary source of this increase. In the pristane-conditioned peritoneum, these cells rapidly form a chronic granuloma on the peritoneal connective tissues. Daily subcutaneous treatment of mice with 0.5 mg of hydrocortisone beginning simultaneously with pristane injection prevents the increase in the peritoneal cell population, granuloma formation, d the production of a conditoned environment. In mice treated with hydrocortisone beginning 3 days after pristane injection, however, neither the peritoneal cell increase nor the production of a conditioned environment is prevented. The intraperitoneal injection of thioglycolate medium at 4-day intervals produces an elevation of the free adherent peritoneal cell population similar to pristane, but does not produce a granuloma or a conditioned environment. The intraperitoneal transfer of thioglycolate-induced adherent peritonel cells to mice treated with pristane and hydrocortisone simultaneously restores the production of a conditioned environment. These findings indicate that the adherent peritoneal cell population is responsible for the conditioning effect, and that the establishment of a resident population of these cells is necessary to produce conditioning.