Electron transfer in the hemoglobin reductase (cytochrome b5) hemoglobin system has been studied as a function of driving force, temperature, ionic strength, and pH. The driving force dependence is consistent with a Marcus’ theory analysis where lambda almost-equal-to 0.9 V. However, the apparent temperature dependence is larger than expected from such an analysis. Analysis of the data suggests that the physiological reaction may proceed via a simple bimolecular collisional mechanism, without preassociation of the protein in a stable complex.