To characterize factors associated with plasma paraoxonase 1 (PON1) activity in healthy Chinese Han population, we carried out the present study, not only taking into account the total set of frequent polymorphisms present in PON1 gene in the Chinese Han population, but also some environmental factors. The -107T/C polymorphism as well as drinking and smoking were independently associated with plasma PON1 activity, determined by rates of phenylacetate hydrolysis. The -107T/C polymorphism had the predominant effect and accounted for 16% of the observed variability in plasma PON1 activity. Alcohol consumption can modulate the effects of cigarette smoking on PON1 activity, and smoking only decreases PON1 activity in non-drinkers. The increase of PON1 activity by drinking or the inhibition of PON1 activity by smoking varies according to PON1 -107T/C genotypes, and the associations were only observed in -107T allele carriers. The results illustrate the complexity of polymorphism-phenotype associations. The observed interactions constitute concrete examples of gene-environment and environment-environment interactions.