Numerous 1,2-benzisothiazole and 1,2-benzisothiazolin-3-one derivatives, variously substituted in the different positions of the molecule, were tested for their in vitro antimicrobial activity. Some corresponding 1,2-benzisoxazoles and 1,2-benzisoxazolin-3-ones were also considered. Several compounds possess a potent and broad antibacterial and antifungal activity, particularly against Gram positive microorganisms, yeasts and dermatophytes. 1,2-Benzisothiazolin-3-ones were found to be the most active substances. On the contrary, the benzisoxazoles and the benzisoxazolin-3-ones considered were devoid of activity. The results obtained are discussed on the basis of structure-activity relationships.