We examined the effects of cerebroventricular injection of synthetic human GH-releasing factor [hGRF-(1-44)] on regulation of GH release in conscious male rats. These results were compared with the direct effects of hGRF on hormone released from dispersed anterior pituitary cells. Administration of two higher doses of hGRF (200 and 2000 ng) into the third ventricle (3V) produced a dose-related increase in plasma GH levels (P less than 0.001). Injection of hGRF into the 3V at two lower doses actually reduced GH release. Infusion of 20 ng (5 pmol) hGRF reduced plasma GH from 5-60 min (P less than 0.005), with a maximum suppression of 66%. The 2-ng (0.5-pmol) dose decreased GH secretion by 45% (P less than 0.05). hGRF stimulated a significant and dose-dependent release of GH from dispersed pituitary cells at concentrations of 10(-10) and 10(-9) M (P less than 0.025). The specificity of GRF for GH control, whether stimulatory or inhibitory, was seen by the failure of GRF to modify PRL, TSH, or LH release. Our results indicate that injection of larger doses of GRF into the 3V produce GH release, but at lower doses, 3V GRF may exert an action centrally to inhibit GH release. We propose that hypothalamic GRF may decrease its own neurosecretion by negative ultrashort loop feedback.