Interleukin-10 (IL-10) is a pleiotropic cytokine that has a variety of downregulatory effects on immunologic and inflammatory processes. Ectopic tumor expression of IL-10 inhibited tumor growth, and local administration of antisense IL-10 significantly reversed the effects of IL-10 transfection in P815 mastocytoma. Tissue inhibitors of metalloproteinase (TIMPs) have been associated with decreased tumorigenesis and reduced metastasis, and TIMPs were increased in the region surrounding P815/IL-10 tumors and reduced in antisense IL-10-treated mice. In addition, the antisense IL-10 group had the largest tumor volume and poorest survival when compared with the P815/IL-10 control or sense groups. In summary, our data suggest that, in a mouse model, antisense IL-10 has substantive effects in reducing IL-10 translation and inhibiting IL-10-mediated TIMP upregulation, and, by doing so, allows IL-10-transfected mastocytoma to grow unchecked. Thus, ectopic tumor expression of IL-10 inhibits tumor growth, and antisense IL-10 administration in vivo reverses this protective effect.