Model peptides, Gly-Gly-Lys-Arg, Arg-Lys-Asp-Val-Tyr, and Pro-Gly-Lys-Ala-Arg were reductively alkylated with [2H6]acetone and sodium borohydride to assess the effects on peptide behavior. Lysine residues were converted to ε-N-isopropyllysine which eluted between phenylalanine and histidine on amino acid analysis. Amino terminal groups were also modified to an extent which depended on the particular peptide (glycine 100%, arginine 30%, and proline 10%-20%). High voltage paper electrophoresis of native and isopropylated peptides showed similar properties except for minor decreases in the mobility of the modified peptides due mainly to increased molecular weight. Isopropyllysine was not an effective substrate for trypsin, and α-N-isopropyl-amino acids did not form dansyl chloride derivatives. These findings should aid in the location, by peptide mapping techniques, of specific modified residues in reductively isopropylated proteins.