The major areas of effort in this project have been (1) to develop new tracers or other approaches for the study of neurotransmitter function in normal and abnormal physiology; and (2) to apply available tracer methodologies to the study of neuropsychiatric disorders. To these ends the following achievements are notable. (18F)-cyclofoxy, an opiate receptor dependent tracer, has been administered to man for the first time. Our initial PET (positron emission tomography) find- ings are that cyclofoxy accumulation is highest in the amygdala, thalamus, caudate and putamen but also apparent in the cingulate, anterior frontal cortex, and cerebellum. Compared to blood flow and glucose metabolic images, visualization of the amygdala is the unique feature of cyclofoxy studies. PET measurements of glucose metabolism are increasing our understanding of the functional activities of the brain in psychiatric disorders. In schizophrenia, the data generated support functional abnormalities of the superior parietai and mid- prefrontal cortices, regions to which the ability to sustain attention is localized to in normals. Part of the functional abnormality in schizophrenia appears to be sensitive to neuroleptic treatment. Furthermore, we observe a similar abnormality in manic- depressive disorder, but not in attention deficit, panic and obsessive compulsive disorders. In contrast, we have observcd an abnormally high metabolic rate in the orbital frontal cortex of obsessive compulsive patients. Thus, the mid-prefrontal cortex abnormality may reflect a vulnerability factor in the development of psychosis.