A new series of indolo[1,2-c]quinazoline derivatives were prepared in good yield through reaction of 2-(o-aminophenyl)indole with a variety of arylaldehydes. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectral studies and elemental analysis. All the title compounds were investigated for their activity against certain strains of Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Streptococcus pyogenes), Gram-negative bacteria (Salmonella typhimurium, Escherichia coli and Klebsiella pneumonia) and pathogenic Fungi (Aspergillus niger, Candida albicans and Trichoderma viridae). Ampicillin and ketoconazole were used as reference compounds. The results revealed that some of synthesized compounds displayed marked activity against all the tested microorganisms.