(ethanol and phenacetin) were added to liver microsomal preparations (all at a concentration of 1 mM) to determine their effects on both the initial rate of reduction and the final absorbance (45W90nm) change. It was found that type I1 compounds inhibited the initial rate by over 50% and also decreased the final absorbance change (i.e. inhibited CO binding to the reduced cytochrome). RI compounds, however, had either no effect or inhibited the initial rate to a lesser degree and barely affected the final 450-490nm absorbance change (Fig. 1). Results from this approach agreed with the preliminary classification of the benzimidazoles into type I1 and RI compounds. It appears that the type of binding of the 2-substituted benzimidazoles is determined by the nature of the substituent in the 2-position. If the 2-position is unsubstituted or contains a primary amino or carboxylic acid grouping, then a type I1 spectrum is observed. However, any other substituent. even a methyl group leads to the observation of a RI spectrum.