Conscious, Long-Evans rats, chronically-instrumented for the direct measurement of intra-arterial and central venous pressures and ascending aortic blood flow (i.e. cardiac output), were given bolus, intravenous doses (4 and 40 pmol) of endothelin-1, -2, or -3 or sarafotoxin S6b in random order. The lower dose of endothelin-1 and -3 and sarafotoxin S6b caused a significant increase in cardiac output. The higher bolus dose of the same three peptides caused initial hypotension and increases in cardiac output, stroke volume and total peripheral conductance. Endothelin-2 did not have these initial effects in all animals. Subsequently, all peptides increased mean arterial blood pressure and decreased cardiac output and total peripheral conductance. Overall the effects of endothelin-1 and sarafotoxin S6b were very similar, consistent with them acting at the same site.