We performed thyrotropin-releasing hormone (TRH) stimulation testing in 18 nondepressed patients with primary degenerative dementia (10 M, 8F; average age +/- SD = 68 +/- 7) and 12 elderly controls (7M, 5F; average age +/- SD = 61 +/- 6). Six patients were retested approximately 2 years later. Initial Mini-Mental State Examination scores for patients ranged from 2 to 28 (average +/- SD = 18 +/- 6) and the scores for the control subjects were all equal to 30. Protirelin (500 micrograms) was injected iv and blood was sampled at 0, 15, 30, 45, 60, and 90 min for thyrotropin-stimulating hormone (TSH) and prolactin (PRL). There were no significant differences between patients and controls in baseline T4, T3 uptake, TSH, or PRL. No significant differences were found between patients and controls for either TRH-stimulated TSH or PRL at all time points. Duration of illness, severity of dementia, and severity of depressive symptoms did not correlate significantly with stimulation test results. There were, however, significantly greater responses in stimulated TSH and PRL for women compared with men in both patients and controls. Upon repeat testing (n = 6), TRH-stimulated TSH and PRL were not significantly different from the initial results.