Objectives: Endothelins (ET-1 and ET-3) may be promoters of tissue remodelling, including fibrillar collagen accumulation. The hypothesis that ET-1 and ET-3 each modify cardiac fibroblast collagen turnover was tested. Methods: Confluent adult rat cardiac fibroblasts were maintained for 24 hours in medium with 0.4% fetal call serum, and varying concentrations of ET-1 or ET-3. Collagen synthesis was measured by ³H-proline incorporation. The synthesis of type I and III collagens was measured by enzyme linked immunosorbent assay (ELISA). The effects of endothelins on collagenase activity were estimated by zymography. Results: ET-1 and ET-3 increased collagen synthesis in a concentration-dependent manner with a maximal 1.7-fold increase (p < 0.001 v control cells). The effects of ET-1 or ET-3 on collagen synthesis were not blocked by PED-3512-PI (10⁻⁶ M). an ET_A receptor antagonist. ET-1 and ET-3 each significantly (p < 0.01) increased the synthesis of both type I and III collagens. ET-1 caused a 5.8-fold decrease in collagenase activity (p<0.01 v control), and this effect was blocked by PED-3512-PI (10⁻⁶ M). ET-3 did not alter collagenase activity. Conclusion: ET-1 and ET-3 increased the synthesis of type I and III collagens, whereas ET-1. but not ET-3, reduced collagenase activity. The effects of endothelins on collagen synthesis in cardiac fibroblasts seem to be mediated through ET_A and ET_B receptors, whereas their effects on collagenase seem to be mediated by ET_A receptors. Cardiovascular Research 1993: 27: 2130-2134