Multiple blood sampling techniques and short-term, timed urine collections were employed before and after luteinizing hormone releasing factor (LRF) administration to 51 individuals on 58 occasions. Correlation of blood and urine per cent responses to LRF were significant for LH (P less than .05) and FSH (P less than .001), indicating that urine measurements provide an adequate means of assessing response to LRF. In 7 patients with basal blood gonadotropin levels below assay sensitivity, urine measurements provided the only means of accurately determining a response to LRF. Per cent response to LRF was negatively correlated with basal LH levels in the urine (P less than .02) but not in the blood. A significant negative correlation between basal levels and per cent response was demonstrated for FSH in blood and urine (P less than .01). Accurate measurement of basal gonadotropins and the expression of LRF responses as per cent increments aided in distinguishing between patients with hypothalamic and pituitary diseases. A marked response to LRF in the presence of very low basal LH levels was found in patients with hypothalamic disorders, a finding revealed only by using urine determinations. Low per cent responses to LRF were seen primarily in patients with pituitary disease, a situation most clearly delineated by blood FSH measurements.