Abstract: Disease response to spot blotch by different varieties of wheat namely K 307, K 9644, K 9162, K 9351, K 9465 and HD 2985 revealed that all the varieties give variable response on disease severity. Among the varieties, minimum disease severity was recorded in K 9351 with the value of 30.07% at 65 days of plant. Biochemical analysis of leaves of different varieties of wheat revealed that the variable amount of phenol and soluble protein content. The maximum with 31.50 and 28.60 mg g–1 of soluble protein and 3.10 and 2.85 mg g–1 of total phenol content was found in K 9351 at 20 and 65 days of plant, respectively. The correlation co-efficient between disease severity and soluble protein and total phenol content at 65 days of wheat varieties revealed that there was negative correlation showing (r) -0.974 and -0.953. The regression equation of soluble protein and disease severity showed that higher regression value, lower disease incidence. It is also cleared that increase amount of total phenol and protein content both are associated with decreases of disease severity and both the parameter are reduced with the increase with age of plant. The RAPD analysis of different wheat varieties revealed that variable number and size of fragments are found among the varieties. The highest numbers of fragments are found in variety K 9351 which is 13. The presence or absence of fragment and their variable size might be the responsible for morphological and biochemical variability along with resistance response to spot blotch.