The rate constants (25 degrees , M(-1) sec(-1)), activation enthalpies (kcal/mol), and activation entropies (e.u.) for the second-order reduction of oxidized clostridial rubredoxin by Ru(NH(3))(6) (2+), V(H(2)O)(6) (2+), and Cr(H(2)O)(6) (2+) at I = 0.10 have been determined or estimated to be 9.5 x 10(4), approximately 1.4, approximately -31 (pH 6.3-7.0); 1.6 x 10(4), 0.1, -40 (pH 3.5-4.5); and 1.2 x 10(3), approximately 0, approximately -44 (pH 3.5-4.0), respectively. Ionic strength dependencies for the vanadium reaction are suggestive of a direct interaction of the reductants with the Fe(SR)(4) (-1) site of oxidized rubredoxin. The results are consistent with outer-sphere mechanisms for all three reductants and an especially high inherent outer-sphere reactivity of rubredoxin. This high reactivity level is attributed to the low activation enthalpy demands of the iron-sulfur site of rubredoxin. Thus, the possibility is raised that the rate of reaction of rubredoxin with its physiological counterparts may be determined largely by the activation entropy demands imposed by the physiological reactant. Evidence is presented in support of an absolute entropy decrease of about 7.5 e.u. on going from oxidized to reduced rubredoxin, which is presumably attributable to the charge increase from Fe(SR)(4) (1-) to Fe(SR)(4) (2-) at the redox site.