The complement pathway is activated during kidney fibrosis and may contribute to renal inflammation, but the underlying mechanisms are unclear. Using a mouse model of kidney injury, Xavier et al. show that platelet-derived growth factor receptor-β-positive pericytes (which are non-immune, interstitial cells) secrete C1q; this complement component is involved in activation of the classical pathway. Global deletion of C3, which is downstream of C1q, reduced fibrosis in mice, suggesting that the complement pathway might represent a novel therapeutic target for the treatment of renal fibrosis.