In the infarcted myocardium, activation of the inflammatory cascade clears the wound from dead cells, whereas stimulating matrix degradation and chamber dilation, thus contributing to the development of heart failure. IL-1 is critically involved in the postinfarction inflammatory reaction and mediates adverse dilative remodeling. We hypothesized that IL-1 may regulate postinfarction repair and remodeling through cell-specific actions on leukocytes and fibroblasts. Flow cytometry demonstrated that in mouse infarcts, early recruitment of proinflammatory Ly6C hi cells expressing IL-1R1, the signaling receptor for IL-1, was followed by infiltration with cells expressing the decoy receptor, IL-1R2. Increased expression of IL-1R2 may serve to terminate IL-1–driven inflammation after infarction. Loss of IL-1 signaling in IL-1R1 null mice globally attenuated leukocyte recruitment, reducing the number of infiltrating Ly6C hi and Ly6C lo cells. Nonmyeloid CD11b− cells harvested during the inflammatory phase of cardiac repair exhibited marked upregulation of chemokines and cytokines; their inflammatory activation was IL-1R1 dependent. Moreover, IL-1β attenuated TGF-β–induced contractile activity of fibroblasts populating collagen pads, attenuated α-smooth muscle actin expression, and stimulated matrix metalloproteinase synthesis in an IL-1R1–dependent manner. The effects of IL-1 on TGF-β responses in cardiac fibroblasts were not due to direct effects on Smad activation, but were associated with endoglin suppression and accentuated expression of bone morphogenetic protein and activin membrane-bound inhibitor, a negative regulator of TGF-β signaling. IL-1 may orchestrate fibroblast responses in the infarct; early stimulation of fibroblast IL-1R1 signaling during the inflammatory phase may prevent premature activation of a matrix-synthetic contractile phenotype until the wound is cleared, and the infarct microenvironment can support mesenchymal cell growth.