Abstract α-Chymotrypsin was used to investigate the reactions of folpet and its decomposition product thiophosgene with nonthiol proteins. Inhibition of enzyme activity by both compounds was correlated with changes in the properties of the protein as determined by polyacrylamide gel electrophoresis. Binding studies using 14C and 35S folpet indicated that the intact fungicide molecule was attached to protein site(s). The protein-fungicide complex(es) became unstable with time, however. The attachment of folpet to α-chymotrypsin, enzyme inhibition, and changes in gel patterns of treated proteins appeared to be pH dependent. These data suggest changes in the catalytically active conformation of treated protein. Possible reaction mechanisms involving folpet and thiophosgene with protein binding site(s) are discussed.