The catechoI-O-methyltransferase (COMT) gene occurs as two polymorphic alleles, which code for a high activity thermostable and low activity thermolabile form of the enzyme. We devised a fast solid-phase minisequencing assay for genotyping theCOMTgene at nucleotide position 544 encoding amino acid residue 158. The method was applied to correlate the genotype of theCOMTgene with the biological activity of theCOMTenzyme. In red blood cells from individuals homozygous for G at nucleotide position 544 coding for Val-158, the activity ofCOMTranged from 0.55–1.03 pmol min-1mg-1protein, and in individuals homozygous for A at position 544 coding for Met-158, the activity ranged from 0.21–0.43 pmol min-1mg-1Heterozygotes showed intermediate activities of 0.20–0.88pmol min-1mg-1. The thermostability (heated/unheated) at 48º C of the high activity form was shown to be about twofold compared to that of the low activity form of the enzyme. By analysing 76 individual samples and three pooled samples representing altogether 3140 individuals using the solidphase minisequencing method, the twoCOMTalleles were shown to be equally distributed in the Finnish population. No statistically significant difference in the frequencies of theCOMTalleles was found when comparing the normal population with a sample of 158 Finnish patients with Parkinson's disease.