Paraoxon and diisopropylfluorophosphate elicit a massive, selective increase in serum β-glucuronidase but not other lysosomal enzymes. The response is not blocked by atropine nor mimicked by neostigmine or carbachol. It is therefore not cholinergically mediated. Removal of the liver, by evisceration, abolishes the response suggesting a role for liver in mediating the organophosphate effect. β-Glucuronidase isolated by affinity chromatography from sera of organophosphate treated rats is catalytically similar to rat liver β-glucuronidase while having a lower isoelectric point. Following intravenous injection, purified rat liver microsomal and lysosomal β-glucuronidase are rapidly cleared from the circulation (t 1 2 = 7 min). In contrast, β-glucuronidase isolated from sera of organophosphate treated rats has a much slower clearance (t 1 2 = 47 min). Removal of the liver, by evisceration, severely reduces the clearance of all the enzyme preparations. Competition experiments with asialofetuin and asialoorosomucoid suggest that liver receptors for asialoglycoproteins do not mediate clearance of β-glucuronidase.