Human serum butyrylcholinesterase (BChE) has been. converted into a stable but less active desensitized form when heated at 45degreesC for 24 h. The desensitized BChE. follows Michaelis Menten kinetics., whereas native enzyme exhibits slightly negative cooperativity with respect to butyrylthiocholine binding. In this study, we investigated the effects of Ni2+, Co2+, and Mn2+ on the desensitized BChE. It is found that all three ions were noncompetitive inhibitors of the desensitized BChE, and K-i values have been determined as 7.816+/-1,060 mM, 48.722+/-4.635 mM, and 84.795+/-5.249 mM for Ni2+, Co2+-, and Mn2+, respectively, In our previous study, these ions were linear mixed-type inhibitors of the native BChE. This finding confirms that desensitized BChE changes to a different conformation than native BChE. From the comparison of Ki values of the trace elements, it can be said that Ni2+ is a more effective inhibitor of the desensitized BChE than Co2+ and Mn2+.