Two aspects of prostaglandin F (PGF) metabolism were assessed in patients with primary affective disorder. For a group of hospitalized patients cerebrospinal fluid PGF was measured by radioimmunoassay and the effects of probenecid and L-tryptophan were determined. For outpatients attending our Lithium Clinic, plasma PGF was measured and the acute and chronic effects of lithium were determined. The results of the studies reveal apparently normal concentrations of PGF in cerebrospinal fluid. These concentrations increase twofold after probenecid, indicating that PGF is transported out of the central nervous system by a probenecid-sensitive active transport system. Evidence for inhibition of PGF synthesis during L-tryptophan treatment was found. The results for outpatient plasma studies suggest no effect on PGF with 12 weeks of lithium treatment, although a slight elevation of plasma PGF with chronic lithium treatment may occur. Specificity of the assay technique as applied to plasma is discussed. This is the first report of the direct measurement of PGF in a psychiatric disorder.