The objectives of this project are to provide a centralized laboratory which can perform specialized antifungal testing required to support clinical trials. This project will also propose guidelines for specialized antifungal testing with objectives of improving the quality of data and reducing the resource required for such testing. This laboratory will provide fungal antigen testing, in vitro susceptibility testing and antifungal drug levels required to support antifungal protocols. This project will also perform developmental studies required to incorporate new tests needed for fungal studies. This project will establish a repository for specimens and organisms to facilitate developmental research within the ACTG and to answer unanticipated questions. All specimens will be saved in the repository for at least one year after completion of a trial. By standardization and centralization of specialized testing, the role of these tests in antifungal therapy can be established with greater certainty. Specific questions which will be addressed are as follows: Does antigen clearance provide a useful independent marker for response to antifungal therapy? Does clearance of antigenemia predict outcome and reduce the frequency of lumbar puncture in anti-cryptococcal trials? Can therapeutic concentrations for antifungal drugs be determined? Does in vitro susceptibility predict response to therapy? Does cross resistance occur with antifungal agents of the same class? Our laboratory has developed evidence supporting a useful role for antigen testing in histoplasmosis and has demonstrated the usefulness of determination of antifungal drug levels when using agents of uncertain bioavailability in ongoing ACTG 084 and 120 evaluating itraconazole for histoplasmosis. Standardization and centralization of this testing to a single reference laboratory has facilitated these accomplishments. Similar standardization and centralization should increase the information obtained from anti- cryptococcal clinical trials. Our laboratory has the experience and resources to provide this centralized testing.