Paraoxonase (PON1) is a serum enzyme that plays an important role in prevention of atherosclerosis and also protects against organophosphate-induced neurotoxicity. PON1 displays a high variability in human populations. In this study, PON1-192 and -55 polymorphisms and correlation to serum PON1 activity were investigated in 132 healthy Iranian individuals from Isfahan province. The genotype frequencies for PON1-192 were approximately 48% (QQ), 42.% (QR), and 10% (RR) and for PON1-55 17% (MM), 48% (ML), and 35% (LL). Thus, the frequencies of alleles R and L were 0.31 and 0.59, respectively. PON1 activity toward paraoxon was markedly affected in both polymorphic populations in the following order QQ < QR < RR genotype for PON1-192 and MM < ML < LL genotype for PON1-55. Neither polymorphism significantly affected PON1 activity toward phenylacetate. The RR/LL individuals had the highest PON1 activity and QQ/MM individuals the least. The QR/ML haplotype was the most frequent seen in Iranians, and the RR/MM and QR/MM haplotypes were absent in this population. In conclusion, the frequencies of PON1-192 and -55 polymorphisms in this Iranian population were different from those seen in other Asian populations from Japan and China but similar to those for European Caucasians.