Reactions of lead cluster cations and anions with acetone have been studied using a homemade reflectron time-of-flight mass spectrometer. Association with acetone to form Pbk(CH3COCH3)n+, high-energy pathway reactions forming PbkCH3+, and intraheterocluster reaction of Pbk(CH3COCH3)n+1+ to give PbkCH3(CH3COCH3)n+ were the main reaction pathways for lead cluster cations with acetone. Decomposition of acetone by Pbk to give PbkCm ions and their further association with acetone, PbkCm(CH3COCH3), were the dominant reactions of lead cluster anions with acetone. Pb7, Pb10, and PbkC5 were ‘magic numbers’ with special structural stabilityin Pbk and PbkCm, respectively. In addition, PbkH, CH2COCH3(CH3COCH3)n and PbkCH2COCH3(CH3COCH3)n were also observed in the reaction of lead cluster anions. Some reaction mechanisms are proposed for these reactions. To investigate the isotope effect for the reaction of lead cluster cations and anions with acetone and to verify the structural assignments of the observed ions, reactions of lead cluster cations and anions with deuterated acetone-d6 were also performed. Copyright © 2002 John Wiley & Sons, Ltd.