The procedures for determining paraoxonase (PON1) status and for determining PON1 genotypes for polymorphisms in coding and important regulatory regions are described. PON1 status is determined by a functional two-substrate analysis of plasma PON1 activities. Differences in catalytic efficiency of the PON1₁₉₂Q and PON1₁₉₂R alloforms result in the clear separation of all three phenotypes at position 192 (Q/Q, Q/R, R/R) and at the same time, the two-substrate analysis indicates activity levels of PON1. Because the enzyme activity levels are as important as the polymorphic genotypes, this two-substrate analysis of PON1 status provides the most relevant information for investigating the association of PON1 genetics with susceptibilities to disease, organophosphorus insecticide sensitivity, and pharmacokinetic status of drug metabolism. Genotyping of polymorphic sites alone fails to provide this important information but can be useful for gene frequency determination and forensic analysis. Analytical procedures for determining PON1 status and genotypes are described.