AbstractA kinetic analysis of cytochrome P450‐mediated desulfuration (activation) or dearylation (detoxication) showed that rat hepatic microsomes have a greater capacity to detoxify and a lower capacity to activate chlorpyrifos compared to parathion. Kinetic curves for the desulfuration of both parathion and chlorpyrifos were biphasic;K m apps of 0.23 and 71.3 μM were calculated for parathion, and 1.64 and 50.4 μM for chlorpyrifos. While phenobarbital (PB) exposure seemed to generally lower theKmapps for desulfuration except for the lowKmactivity on chlorpyrifos, the results were not statistically significant. While the lowKmactivity contributed 44 and 60% of the control Vmaxfor parathion and chlorpyrifos, respectively, it contributed 50 and 17% in PB‐treated rats. These studies have indicated the presence of a lowKmactivity capable of functioning at very low substrate concentrations. A single dearylationK m appwas calculated, 56.0 and 9.8 μM for parathion and chlorpyrifos, respectively. Phenobarbital exposure seemed to raise theK m apps of dearylation; however, again, the results were not statistically significant. While numerous biochemical factors contribute to the overall toxicity levels of phosphorothionate insecticides, thein vitroefficiencies of hepatic microsomal desulfuration and dearylation of parathion and chlorpyrifos correspond to the acu