A series of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine derivatives 4a-k were synthesized by the reaction of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine with various aldehydes. The newly synthesized compounds were characterized by elemental analyses, UV-visible, FT-IR and 1H NMR spectral studies. All compounds were evaluated their in vitro antimicrobial activity against clinically isolated strains i.e., Bacillus subtilis, Staphylococcus aureus, Xanthomonas campestris, Escherichia coli, Fusarium oxysporum. Compounds 4f, 4g, 4h and 4i exhibited good antimicrobial activity when compared with other compounds in the series against tested pathogenic bacterial and fungal strains