Prolactin (PRL) levels were investigated in patients with major depressive illness and in healthy subjects. Basal and postdexamethasone levels were measured in 27 patients, and levels after thyrotropin-releasing hormone (TRH) stimulation (delta PRL) were measured in 22 patients. Basal and delta PRL were also determined in 64 age- and sex-matched healthy subjects. Both basal and postdexamethasone PRL levels were normal in depressed patients, with the postdexamethasone levels in particular showing no correlation to postdexamethasone cortisol concentrations. One milligram oral dexamethasone did not influence 4:00 PM PRL levels in 15 healthy subjects. delta PRL was significantly elevated in both male and female patients. These increases were not correlated with severity of illness and are difficult to interpret owing to the complexity of the PRL regulatory system. No significant correlations were found between basal or post-TRH PRL and cortisol, thyroid-stimulating hormone (TSH), thyroid hormones, gonadotropins, or estradiol in the patients. However, surprisingly significant positive correlations between basal PRL and basal cortisol, T4 and reverse T3 occurred in healthy subjects. It is as yet unclear how this finding can be explained and what relevance it has. Women tended to have higher basal PRL concentrations than men, but the difference was not significant in either group. delta PRL was significantly higher in women than in men in both patients and controls. No significant influence of age was found.