Rate constants for the reaction of (haloalkyl)-1,5-diazabicyclo[3.3.0]octadienediones (halo-9,10-dioxabimanes) with the tripeptide thiol, glutathione (GSH), are reported. Certain bromobimanes are fluorescent labeling agents for thiols. Monohalobimanes and glutathione react by either displacement or reduction (replacement of alkylhalogen by hydrogen). Dihalobimanes react with glutathione in two stages: (1) displacement of a halogen by GS− yields a monobromo-monoalkylthio intermediate, which reacts further either by (2a) an intermolecular displacement pathway, forming a bis-substituted product, or by (2b) an intramolecular displacement (neighboring group) pathway, the resulting sulfonium ion reacting further as described elsewhere.13 Reduction is also observed for dihalobimanes. syn-(BrCH2,CH3)(CH3,CH3)B is slightly more reactive than the corresponding anti derivative and 10 times as reactive as benzyl bromide. Either a-methyl substitution or replacement of bromine by chlorine seriously diminishes the rate constants for reaction with nucleophiles. The syn-(bromoalkyl,chloro)bimanes are more than 10 times as reactive as the syn-(bromoalkyl,methyl)bimanes but are also more susceptible to reduction by glutathione.