The plasma of dogs afflicted with mammary carcinoma was perfused through chambers bearing Staphylococcus aureus Cowan strain I in an attempt to remove tumor-promoting, immunosuppressive immune complexes from the peripheral blood of these animals. In this canine model of spontaneous mammary carcinoma, reduction of breast and/or soft-tissue tumor (posttreatment size equal to 0 to 50% of pretreatment tumor size) was observed in five of the ten animals so treated. Immune complexes capable of blocking lymphocytotoxicity were measured pre- and postimmunoadsorption; removal was more efficient in the five responders (four of six complexes) than in nonresponders (one of ten complexes), although statistical significance was not attained. The reduction of tumor size seen in soft-tissue sites was not always accompanied by a similar reduction of tumor size in visceral sites, and surgical resection of residual soft-tissue tumor nodules remaining after immunoadsorption treatment was required to achieve a complete response in two responding animals. No significant decrease in tumor size was observed in the control group, perfused without immunoadsorbent, nor in five additional tumor-bearing animals infused with normal dog plasma which had been passed through S. aureus Cowan strain I-containing chambers. These data indicate that immunoadsorption of tumor-bearing host plasma can result in reduction in size of canine mammary adenocarcinoma but that the response is dependent on the site of the tumor (s.c. versus visceral) and may require utilization of other modalities to achieve a complete disappearance of the tumor.