&NA;Bosentan (RO 470203), a sulfonamide, is a competitive endothelin (ET) receptor antagonist that antagonises both endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Bosentan is derived fromRO462005 andwas undergoing phase III investigation with Roche in Switzerland for disorders associated with vasoconstriction. A phase III, multicentre trial for congestive heart failure (CHF) [REACH-1 trial] was terminated early as a result of liver toxicity at high doses. Development was suspended while Roche was seeking a development partner for bosentan. Actelion, a Swiss research company, has partnered with Roche for the development of bosentan in the treatment and/or prevention of diseases relating to the vascular endothelium. Actelion is planning to initiate a large phase III trial in patientswithCHF during the second quarter 1999. TheREACH-II trial is being conducted at the University of Alberta, Canada. The agreement between Roche and Actelion allows Roche to reclaim development of bosentan after completion ofActelion's phase III trial. The trialwill be investigating lower doses of bosentan than the original REACH-1 trial, and will involve a teamof liver function experts.Bosentan appears to be in clinical investigation for ischaemic heart disorders.Researchers at the Kagawa Medical University in Japan are preclinically investigating the effects of bosentan in the prevention of reperfusion injury in animals undergoing heart transplant.Researchers at St Vincent's Hospital in Australia are preclinically investigating bosentan as a treatment for prevention of chronic allograft rejection for aortic transplantation.Bosentan, a competitive ET antagonist, represents a novel therapeutical approach, since there is an evidence that ET may contribute to hypertension and associated cardiovascular disorders. Orally bioavailable bosentan is suitable for once daily administration in hypertension, with efficacy similar to that of enalapril. In CHF, a twice daily dose has been used in trials. Bosentan is well tolerated. The reported adverse events are associated with high doses of the drug.