PRL was measured radioimmunologically in plasma and cerebrospinal fluid (CSF) samples obtained simultaneously in 31 patients with various neurological or infectious, but non-endocrine diseases (group A), 12 patients (7 pregnant women and 5 newborns) with physiological hyperprolactinemia (group B),10 psychiatric patients with pharmacologically induced hyperprolactinemia (group C) 12 normoprolactinemic patients with pituitary adenoma and suprasellar extension (SSE) (group D), And 14 hyperprolactinemic patients with pituitary adenoma with and without SSE (group E). Plasma PRL and CSF PRL concentrations (ng/ml, mean and range in brackets) of the various groups were: group A, 6.2 (1.3-14.5) and 1.3 (0.6-4.7); group B, 85.2 (31-200) and 13.2 (3-28); group C, 54.3 (3.5-160) and 6.5 (0.7-18); group D, 17.2 (5.4-30) and 9.7 (2.7-34); and group E, 2,529 (115-10,000) and 1,449 (6-13,000). The plasma to CSF concentration ratios (mean and range in brackets) were: group A, 5.2 (1.4-13.0); group B, 7.0 (2.9-10.3); group C, 7.3( 3.9-11.3); group D, 2.6 (0.9-7.1); and group E, 10.9 (0.2-34.9). The ratio was greater than 3 in 87% of the non-tumor patients; in 42% of the tumor patients the ratio was less than 3. The correlation between plasma and CSF PRL levels of all 53 subjects without a pituitary tumor (groups A, B, and C) was positive (r=0.9097; P=0.00001); in the 26 tumor patients (groups D and E) the correlation was also positive (r=0.7141; P=0.00002). These results indicate that 1) PRL is a normal constituent of CSF, 2) the CSF PRL level is a function of the plasma level, 3) detectable, or even high, CSF PRL levels per se are not indicative in the presence of a pituitary tumor, with or without SSE, and 4) abnormally low ratios may be found in patients with a pituitary tumor with SSE.