The antiproliferative activity of aconitylated (AIFN) and succinylated (SIFN) derivatives of recombinant interferon- alpha2b (IFN-alpha2b) was examined. Acylation of IFN-alpha2b was performed by succinic and cis-aconitic anhydrides. Antiproliferative properties of AIFN and SIFN were studied in vitro on the CaOv cell line, highly sensitive to IFN, and on the SW-480 cell line, with low sensitivity to IFN-alpha2b. Acylation of one lysine in the IFN-alpha2b molecule with cis-aconitic or succinic anhydride resulted in a 3-3.5-fold increase of its antiproliferative activity on CaOv cells. The highest antiproliferative activity of acylated IFN-alpha2b on SW-480 cells was observed for both AIFNs and SIFNs with three modified lysine residues. In conclusion, aconitylated and succinylated IFNs may be useful antiproliferative agents for cancer treatment.