This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 ± 9.0 (SD) versus 4.4 ± 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 ± 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.