Plasma prolactin levels were determined for 8 patients (7 males and 1 female) who reported an average of 3.7 years of cocaine abuse. The mean prolactin level for these 8 patients 24 to 72 hours following admission to the hospital was 20.58 (S.E. +/- 3.2) ng/ml. Hyperprolactinemia (greater than 20 ng/ml) was detected in 4 patients and 3 others had high borderline prolactin levels. Only 1 patient had a normal prolactin value at the time of admission to the hospital. The mean prolactin level obtained prior to the patients' discharge from the hospital was 31.7 (S.E. +/- 5.3) ng/ml. Five of the 8 patients had an increase in prolactin levels between time of admission and discharge from the hospital. The mean increment in plasma prolactin levels for these 5 patients was 15.5 (S.E. +/- 4.2) ng/ml (P less than .02). Two patients who had significant hyperprolactinemia (greater than 50 ng/ml) at the time of discharge from the hospital reported self-administering the highest cocaine dose (6-8 gm per week) of the 8 patient cohort. Since cocaine blocks dopamine reuptake and prolactin secretion is regulated, in part, by dopaminergic inhibitory mechanisms, cocaine withdrawal may induce rebound supersensitivity of prolactin secretion. Findings obtained in this study suggest that cocaine-related derangements in prolactin secretion may be a biologic marker of a protracted cocaine abstinence syndrome.