The antiviral activity of native and esterified whey proteins fractions (alpha-lactalbumin, beta-lactoglobulin, and lactoferrin) was studied to inhibit tomato yellow leaf curl virus (TYLCV) on infected tomato plants. Whey proteins fractions and their esterified derivatives were sprayed into TYLCV-infected plants. Samples were collected from infected leaves before treatment, 7 and 15 days after treatment for DNA and molecular hybridization analysis. The most evident inhibition of virus replication was observed after 7 and 15 days using alpha-lactoferrin and alpha-lactalbumin, respectively. Native and esterified lactoferrin showed complete inhibition after 7 days. On the other hand, native beta-lactoglobulin showed inhibition after 7 and 15 days whereas esterified beta-lactoglobulin was comparatively more effective after 7 days. The relative amount of viral DNA was less affected by the esterified alpha-lactalbumin whereas native alpha-lactalbumin inhibited virus replication completely after 15 days. These results indicate that native or modified whey proteins fractions can be used for controlling the TYLCV-infected plants.