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The vine decline of cantaloupe plants, Monosporascus cannonballus is a worldwide disease particularly in arid and semi-arid regions under warm and hot weather conditions. It has become the main limiting factor for cantaloupe production in N. Sinai, Egypt during the last few years. Control practices of this disease have not been successful. Therefore, the effect of different methods (chemical and/or biological) to control Monosporascus wilt and root rot of cantaloupe were studied both in vitro and in vivo. Three fungicides (Topsin- M 70, Rizolex-T and Vitavax 200) at five concentrations (10, 50, 100, 500 and 1000 ppm) were assayed against M. cannonballus on CMA medium. The effect of antagonistic fungi and/or bacteria, i.e. Trichoderma album and Bacillus megaterium were also tested against M. cannonballus growth in vitro. T.album isolate significantly suppressed the growth of M. cannonballus and it subsequently overgrew the pathogen. On the other hand, B. megaterium was less inhibitive to M cannonballus. Field trials were carried out at North Sinai under natural infection during 2008 and 2009 growing seasons. Soil drenching with the tested fungicides, e.g. Topsin- M 70, Rizolex - T and Vitavax 200 was applied at three intervals, i.e. 15, 30 and 45 days after transplanting. The bio fungicides Bio-Zeid and Bio-Arc were also applied by soil drenching two days alter the application of the chemical fungicides. Each plant received 250 ml of the tested bio fungicide solution. Application of Topsin- M 70 and Bio-Zied was the best combination for controlling vine decline disease and it resulted in the highest total plant fresh weight (gm) and leaf area (LA)/plant.