A one-pot, three-component, solution-phase synthesis of 2,3-disubstituted and 2,3,5-trisubstituted 4-thiazolidinones is described. Poly(styrene-co-divinylbenzene)-supports functionalized with tris(2-aminoethyl)amine and 2-amino-ethanethiol are used to remove excess reagents from the desired product upon completion of the reaction. Simple filtration followed by concentration provides products of sufficient purity for biological evaluation. This approach has been used for a parallel combinatorial generation of a library of multisubstituted 4-thiazolidinones.