To investigate whether anterior pituitary function is disturbed in chronic alcoholic men after a period of alcoholic abuse, TSH and PRL secretagogues were given to such patients in the acute and late withdrawal states (1 and 8 days after admission to hospital, respectively). The TSH and PRL responses were compared with those obtained in a group of control patients without a history of alcohol abuse. Twenty five micrograms of TRH, injected iv in six alcoholic men during acute withdrawal, raised TSH by 1.6 +/- 0.8 (SEM) microU/ml and PRL by 18 +/- 7 ng/ml. In the seven control patients the corresponding responses were significantly larger (7.8 +/- 1.4 microU/ml, P less than 0.01; and 56 +/- 10 ng/ml, P less than 0.02, respectively). When the alcoholics were reinvestigated in the late withdrawal state their TSH and PRL responses increased significantly to 2.9 +/- 1.1 microU/ml (P less than 0.05) and 41 +/- 9 ng/ml (P less than 0.05), respectively. To determine whether dopaminergic inhibition contributed to the reduced TSH and PRL responsiveness in the acute withdrawal state, six additional chronic alcoholic men were tested with oral metoclopramide. This drug, which has dopamine D2-receptor blocking properties, induced similar PRL responses (7- to 8-fold PRL increments) in the acute and late withdrawal states but did not alter TSH. Furthermore, TRH, injected 90 min after oral priming with metoclopramide in six additional alcoholics, elicited TSH and PRL increments in the acute withdrawal state which did not differ significantly from those obtained in the late withdrawal state (TSH, 3.5 +/- 0.9 vs. 4.1 +/- 1.2 microU/ml; PRL, 27 +/- 3 vs. 24 +/- 6 ng/ml). These findings suggest that dopaminergic inhibition of the thyrotrophs and lactotrophs may be responsible for the blunted TSH and PRL responses to TRH during the acute withdrawal period in chronic alcoholic patients.