The long-term objective of this research is to study the role of cyclooxygenase products of arachidonic acid metabolism in tumor growth and metastasis. The specific aims are: (1) to determine the effects of cyclooxygenase inhibitors on the growth and metastasis of murine mammary adenocarcinomas and (2) to define the interactions between tumor-associated cyclooxygenase products and antitumor immune effector functions. We have now shown that cyclooxygenase inhibitors reduce the spontaneous metastasis of these tumors and that this effect may be mediated by increasing the susceptibility of these tumor cells to killing by both macrophage and natural cytotoxic effector cells. These studies will focus on determining the effects of cyclooxygenase inhibitors on the nature of host infiltrates within tumors and evaluating the effect these inhibitors have on immune effector cells. Defining the role of these naturally-occurring products in tumor growth and understanding how these products affect immune function will provide a rational basis for designing immunotherapeutic agents. (HF)