Somatic symptoms in the premenstrual syndrome (PMS) may have an etiology separate from that of the mental symptoms. A disturbance in mineralocorticoid action has been discussed, as mineralocorticoids regulate water balance. Desoxycorticosterone (DOC) is interesting, as it has mineralocorticoid effects and is a precursor to the neurosteroid 5 alpha-pregnan-3 alpha,21-diol-20-one (THDOC). THDOC is a steroid with direct benzodiazepine-like effects on the GABA-A receptor in the brain that is metabolized from DOC within the brain and in the periphery. Ten women with PMS having swelling as a major symptom and eight controls were recruited. They marked, on a validated visual-analog scale, three physical symptoms every evening during one menstrual cycle in conjunction with giving blood samples for progesterone and DOC measurements. DOC showed menstrual cycle-linked variation correlating with progesterone. There was no difference in plasma DOC concentrations between patients and controls. The symptoms reached a maximum 1-3 days before the onset of menstruation, with a delay of 3-6 days after the hormone peak. DOC was less strongly correlated with the symptoms than progesterone. These results do not support the hypothesis that DOC is involved in the etiology of physical symptoms in PMS or that physical and mental symptoms have separate etiologies.