To be clinically useful, antimicrobics must attack molecular sites or functions that are either unique to the parasite or are more vulnerable in the parasite than in the host. Resistance to antimicrobics, as encountered clinically, is either native, i.e., manifest at the very first exposure of the parasite to the antimicrobic, or acquired. Acquired resistance may be either non-infectious or infectious in nature. Elucidation of mechanisms of both native and acquired resistance will be pursued with antibacterial and antifungal agents. Assessment will be made with: 1) chloramphenicol--acetylation capability of clinical isolates of Salmonella typhi and Shigella flexneri resistant to chloramphenicol by an R factor: 2) amphotericin B--stability of amphotericin B and its methyl ester; in vitro susceptibility testing with both drugs. 3) miconazole--study of the basis for obfuscation of antifungal activity by conventional, undefined culture media; evaluation of resistance among clinical isolates of fungi.