A series of new 4-thiazolidinone derivatives were synthesized and evaluated against diverse DNA- and RNA-viruses in mammalian cell cultures. Some of the compounds were found to exhibit moderate antiviral activity. 3-Propyl-2-[((6-(4-chlorophenyl)imidazo[2,l-b]thiazol-3-yl)acetyl)hydrazono]-5-methyl-4-thiazolidinone 13, displayed modest yet consistent activity against three strains of influenza A virus, including the 2009 pandemic virus A/H1N1 Virginia/ ATCC3/2009 (cytotoxicity >100 mu M). Compounds 6 and 11 displayed activity against vesicular stomatitis virus in HeLa cells (antiviral EC50 values of 9 (cytotoxicity 100 mu M) and 2 mu M (cytotoxicity 20 mu M), respectively). Neither of the compounds was active against HIV.