Human paraoxonase (PON1) is an enzyme associated to high-density lipoprotein (HDL) particles that protects against oxidative damage to both low-density lipoprotein (LDL) and HDL. The enzyme is also involved in the hydrolysis of highly toxic metabolite from organophosphate pesticides. In the present study, the distribution of the PON1 polymorphisms at position -108 in the promoter region and at positions 55 and 192 in the coding region, in the Panamanian population (n = 187) was determined. The genotype of each individual was determined by PCR-RFLP. The genotype frequencies at position 55 were: LL 0.631, LM = 0.331, and MM = 0.037; frequencies at position 192 were: QQ = 0.331, QR = 0.497, and RR = 0.171; and the frequencies at position -108 were: CC = 0.428, CT = 0.428, and TT = 0.117. The highest allele frequencies were: Q = 0.581, L = 0.796 and C = 0.655. However, the Amerindian Panamanian group, Gnöbé Bugle, presented a low frequency for the -108CC genotype (0.125), which might be associated to a higher risk to organophosphate pesticides poisoning. Arylesterase and diazoxonase activities of PON1 were determined in samples of the Caucasian and Black Panamanian population. The most frequent haplotype in the whole population was -108CC/55LL/192QR; this haplotype was the second most frequent in Black Panamanians and the most frequent in Caucasian Panamanians. The arylesterase activities for this haplotype were 116.16 U/mL and 146.30 U/mL in Black and Caucasian Panamanians, respectively. Diazoxonase activities were 10.09 U/mL and 11.25 U/mL in the same groups, respectively. Relationships between the arylesterase activity of PON1 and these polymorphisms are discussed.