Monoamine oxidase B (MAO-B) is implicated in the cause of Parkinson's disease (PD) because of its role in metabolizing the neurotoxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine, and forming H,02 during dopamine metabolism. Altered MAO-B activity has been observed in PD platelets. Polymerase chain reaction was used to amplify a portion of the MAO-B gene. Polymerase chain reaction products were screened with restriction enzymes to identify fragments useful for single-stranded conformational polymorphism analysis. A single-stranded conformational polymorphism was identified in an MAO-B polymerase chain reaction product after Hae 111 digestion. One hundred twenty-one control individuals were allelotyped with frequencies of 0.45 and 0.55 for alleles 1 and 2, respectively. Frequencies of 0.62 and 0.38 (1 and 2, respectively) were observed in a population of 46 patients with PD. The presence of MAO-B allele 1 is associated with a relative risk for PD of 2.03-fold (confidence interval, 1.44-2.61; p < 0.02). For comparison, a monoamine oxidase A polymorphism was used to determine allelic frequencies in these same populations and no statistically significant differences were found. These results suggest that an inherited variant of MAO-B may be involved in a genetic predisposition for PD.