The secretion and activation of TGF-β1 in the conditioned media (CM) of cultured HSC was examined using a variety of ELISA based techniques. The effects of inhibiting TGF-β1 with an isoform specific neutralising antibody, both in vitro and in vivo model of fibrosis, were investigated and compared with the effects of a pan TGF-β1 neutralising antibody. CTGF and mRNA and protein expression was examined in fibrotic human and rat liver and in activated HSC, using a variety of techniques. The effects of relaxin on cultured HSC and in and in vivo model of hepatic fibrosis were examined. It was demonstrated that cultured HSC secrete and activate TGF-β1 without accessory cells. The addition of exogenous plasmin or plasminogen increased the amount of both active and latent TGF-β1 in the CM, this being inhibited by the serine protease inhibitors aprotonin, α2-antiplasmin and -(2-amino-ethyl) benzenesulfonyl fluoride. Furthermore, the addition of the uPA inhibitor amiloride also reduced active and total TGF-β1 levels. CTGF is a profibrotic cytokine which is a TGF-β1 inducible product, potentially contributing to the profibrotic effects of TGF-β1. I demonstrated that CTGF expression increases in human fibrotic liver disease and in activated HSC. I also showed that CTGF mRNA and protein expression in activated HSC were stimulated by TGF-β1. However, in an in vivo model, inhibiting TGF-β1 activity with a neutralising antibody did not reduce hepatic fibrosis. In cultured HSC, blocking all TGF-β1 isoforms led to a greater reduction in collagen secretion than inhibiting TGF-β1 alone. Furthermore, I demonstrated that HSC secreted TGF-β3 and that this isoform may have similar effects to TGF-β1. Exposure of HSC to recombinant relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition, with a parallel decrease in TIMP-1 and -2 secretion and TIMP-1 mRNA expression. Following liver injury, relaxin treated rats had decreased hepatic collagen, indicating that relaxin has antifibrotic effects. In conclusion, these results demonstrate that although HSC produce and activate TGF-β1 autonomously through a plasmin-dependent mechanism, other isoforms of TGF-β may contribute to fibrogenesis in the liver.