The synthesis and in vitro antimicrobial activity of 5-substituted 2-(3-pyridyl)benzoxazoles (3-7) is described for some Gram-positive and Gram-negative bacteria and the yeast Candida albicans. The compounds 3-7 exhibited significant activity against the screened microorganisms, having MIC values between 25 and 12.5 mu g/ml. Quantum-chemical calculations were performed for the compounds 1-10, in order to observe some feasible structure-activity relationships. These theoretical observations, calculated for the description of the mechanism of interactions at the molecular level, revealed that the electrophilic superdelocalizability of the nitrogen atom (S-N(E)) in the oxazolo moiety of the benzoxazole ring is related to the activity. The results obtained from the theoretical calculations and the observed MIC values shaw that 2-(3-pyridyl)- and 2-phenylbenzoxazole derivatives exhibit bio-isosteric effects for antimicrobial activity. Additionally, substituents at position 5 on the fused heterocyclic system contribute to the activity constructively or destructively depending on the type of microorganism screened.