The effect of 1-methyl-4-phenyl-pyridinium (MPP+), the main toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism-causing neurotoxin, upon the activity of nicotinamide adenine dinucleotide (NADH) cytochrome c reductase (EC 1.6.99.3) and upon that of glutathione reductase (EC 1.6.4.2) was monitored spectrophotometrically. For the cytochrome c reductase, the increase in absorbance of reduced cytochrome c was measured at 550 nm; for evaluating glutathione reductase, the absorbance of nicotinamide adenine dinucleotide phosphate (NADPH) was followed at 340 nm. MPP+ but not MPTP reversibly inhibited NADH cytochrome c reductase, but not glutathione reductase. This may be a direct mechanism of cell toxicity by this neurotoxin.