Hypertensive cardiac hypertrophy is associated with collagen accumulation in the myocardial interstitium. Myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, factors that regulate collagen synthesis in cardiac fibroblasts are not fully elucidated. The purpose of this study was to investigate the effect of angiotensin II (Ang II) on collagen synthesis by cultured rat cardiac fibroblasts. A 24-hour stimulation of cardiac fibroblasts with Ang II increased their collagen synthesis in a dose-dependent manner. This effect was blocked by the Ang II receptor antagonist, saralasin. Ang II neither affected the proportion of collagen types nor induced DNA synthesis. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats (SHR) was greater than that from normotensive Wistar-Kyoto rats. The responsiveness of collagen production to Ang II was significantly enhanced in cardiac fibroblasts from SHR. These results indicate stimulatory actions of Ang II on collagen synthesis in cardiac fibroblasts, enhanced collagen production in cardiac fibroblasts from SHR, and the hyperresponsiveness of cardiac fibroblasts from SHR to Ang II stimulation. Thus, Ang II may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.