A personal computer (PC)-based expert system developed to monitor the appropriateness of antimicrobial therapy is described. Susceptibility test data and antimicrobial therapy data are downloaded daily from the microbiology department and pharmacy department computer systems. Relational database software allows for the indexing, sorting, and manipulation necessary for analysis. The expert system accomplishes its analyses using (1) databases of organisms, antimicrobial drugs, and susceptibility cutoff values, (2) programs for evaluating pathogenicity and therapy, and (3) algorithms that determine the timing and sequence of the analysis. System output consists of discrepant therapy reports that indicate that no therapy is being given despite the presence of pathogens, that the pathogens isolated are resistant to the therapy being given, that the therapy cannot be matched with susceptibility data on the isolates, or that the therapy was discontinued too quickly. The expert system has been in continuous operation at an 800-bed referral hospital since July 1991. During an 11-month period, the system generated 1538 discrepant therapy reports. The percentage of isolates resulting in reports varied substantially with the source of the isolate. Therapy was more likely to be improved when the physician was contacted about the potential problem indicated by the report than when the physician was not contacted. A PC-based expert system using data from unlinked pharmacy and microbiology computer systems automatically evaluated the appropriateness of antimicrobial drug therapy in light of susceptibility test data.