Shock, a common and frequently fatal manifestation of gas gangrene caused by Clostridium perjringens, is probably mediated by extracellular toxins. Previous studies implicating α-toxin as the major lethal factor were frequently done with preparations contaminated with a second lethal factor, θ-toxin. We purified α- and θ-toxins from C. perjringens and demonstrated that both were lethal to mice. We investigated the effects of these purified toxins on cardiovascular function in intact rabbits; both toxins caused profound hypotension and bradycardia within 40 min. Reduced cardiac output preceded the development of hypotension and bradycardia. Purified α-toxin produced a dose-dependent reduction in myocardial function in isolated rabbit atrial preparations. Purified θ-toxin did not directly inhibit myocardial function. Shock induced by a-toxin may be partly mediated by direct depression of myocardial function. θ-Toxin reduced cardiac output in intact animals but had no direct effects on isolated heart preparations at concentrations that induced shock in intact animals. These data suggest that θ-toxin-induced shock could be mediated by an endogenous myocardial depressant factor.