Two greenhouse experiments were conducted in 2008-2010 at College of Agriculture, Shiraz University, Iran to evaluate the effectiveness of changes in protein content, peroxidase activity, phenolic compounds, free amino acids content and proline in response to wheat streak mosaic virus (WSMV) infection, in screening resistant bread wheat (Triticum aestivum L.) genotypes. Fifteen wheat genotypes consisting of WSMV tolerant, intermediate and susceptible genotypes were grown in two randomized complete designs with three replications. The experiments only differed with respect to their inoculation (either infected or non-infected). The results indicated that viral infection increased the total protein and peroxidase activity of leaves in tolerant genotypes but viral infection decreased them in susceptible genotypes. Phenolic compounds increased in all infected genotypes but these increases are the highest in tolerant genotypes as compared to intermediate and susceptible ones. Viral infection reduced free amino acids in genotypes in general. The changes in proline content did not show a typical trend in tolerant, intermediate or susceptible genotypes. The analysis of variance indicated that the linear regression of leaf damage rating on the changes in total protein, peroxidase activity and phenols in the leaf was significant but the linear regression of leaf damage rating on the changes in free amino acids and proline in the leaf was not significant. Our results demonstrate the changes in total protein, peroxidase activity and phenolic compounds in a genotype could be used as suitable biochemical markers for assessing the WSMV tolerant wheat plants when grown under infected condition.