The goal of this program is to develop a compact accelerator mass spectrometry (AMS) system dedicated to measuring ultra-low quantities of carbon-l4 and tritium in labeled biological samples. The instrument will have a sensitivity 2-3 orders of magnitude higher than that of liquid scintillation decay counters and will allow the measurement of carbon-14 concentrations at or below naturally occurring levels in modern samples. The labeling of biologically active molecules with carbon-14 and/or tritium is a powerful and widely used technique for the study of molecular kinetics in vivo. The high sensitivity afforded by AMS allows the fate of human carcinogens, mutagens and toxins to be studied on the molecular level at extremely low levels of exposure. Existing AMS systems utilize large, expensive tandem accelerators and are generally not available to biomedical researchers. We propose to develop an innovative low-energy AMS instrument compatible with installation and operation in a biomedical research laboratory. The availability of this instrument will greatly expand the number and type of studies which can be conducted using 14C and tritium radiolabels. PROPOSED COMMERCIAL APPLICATION: The AMS instrument developed in this program will have widespread commercial application. Researchers studying carcinogenesis, metabolism and drug effects would benefit greatly from the availability of an ultra-sensitive instrument for the quantitation of 14C and tritium in biological samples. The cost, size and operating requirements of the proposed instrument will be compatible with installation at major biomedical research center.