he important question of how many forms of P450 exist in liver was hotly contested in the early 1970s. It had been widely recognized that administration of various inducers of P450, typified by phenobarbital and 3-methylcholanthrene, altered drug metabolism profiles and increased or altered the carbon monoxide absorption peak attributed to P450, but it was unclear whether this was due to changes in the protein or to changes in the membrane environment. Although this indirect evidence for multiple forms was provided as early as 1966 by the Sato and Mannering laboratories (Imai and Sato, 1966; Sladek and Mannering, 1966), the difficulty of purifying P450 from microsomes made proof difficult.