The metabolism of phencyclidine (PCP) was examined in the isolated perfused lung (lPL), lung microsomes, and liver microsomes of rabbits. The concentration of PCP in the IPL perfusate decreased rapidly with concomitant increases in the concentrations of PCP metabolites. The total rate of PCP metabolite appearance in the perfusate of the IPL was 77.4 nmol/lung/min. The apparent Vmax of PCP metabolism by the lung and liver microsomes were 1.52 and 22.9 nmol of PCP metabolised per mg of microsomal protein per min, respectively. Extrapolated to the whole lung, the apparent Vmax of PCP metabolism by lung microsomes was equivalent to 78.6 nmol of PCP metabolized per lung per min, essentially the same as that for the IPL.