This study was carried out to identify germplasms with multiple disease resistance for wheat improvement. Using field and artificial inoculation tests, reactions of 28 synthetic wheat accessions from CIMMYT to cereal cyst nematodes (Heterodera avenae and H. filipjevi), sharp eyespot (caused by Rhizoctonia cerealis), stripe rust and leaf rust (caused by Puccinia striiformis and P. recondita, respectively) were determined. Various levels of resistance were observed in reaction to these pathogens. Lines C2 and C20 were resistant but lines C5, C10, and C25 were susceptible to all the four diseases tested. Eight lines displayed resistant reaction to both species of Heterodera. However, some lines were only resistant to either H. avenae or H. filipjevi. The synthetic wheats tested exhibited good resistance to sharp eyespot, and 19 lines showed resistant reaction. Nine lines were resistant to P. striiformis races CY30, CY31, CY32, and CY33, and 5 lines were resistant to both P. triticina races of THT and PHT.