Human serum paraoxonase (PON1) hydrolyses diazinonoxon, the active metabolite of diazinon, which is an organophosphate used in sheep dip. In a case-referent study, 175 farmers with ill health that they attributed to sheep dip nominated 234 referent farmers who also dipped sheep and whom they believed to be in good health. We calculated odds ratios for polymorphisms in PON1 at positions 192 and 55, and for PON1 activity with diazinonoxon as substrate. Cases were more likely than referents to have at least one R allele at position 192 (glutamine to arginine aminoacid substitution; odds ratio 1.93, 95% CI 1.24-3.01), both alleles of type LL (1.70, 1.07-2.68) at position 55, and to have diazoxonase activity below normal median (1.77, 1.18-2.67). Our results support the hypothesis that organophosphates contribute to the reported ill health of people who dip sheep.