To clarify the role of somatostatin (SRIF) in pulsatile GH secretion, profiles of the hormone release from intact anterior pituitaries of male rats were examined in an in vitro perifusion system. Infusion of human (h) GRF (0.1 microM) into the perifusion system for 10 min stimulated GH release, which peaked within 30-40 min. Two hours after the first stimulation, when basal GH release had not yet fallen to the original levels, the response to a second hGRF stimulation was attenuated to as low as 47.7 +/- 10.0% (+/- SE) of the first response. However, when GH release after the first stimulation had returned to the basal level after the first stimulation had returned to the basal level after perifusion with the medium for 3 h, the second response to hGRF was restored to a level similar to that of the first response. In contrast, when SRIF (0.1 microM) was infused for 50 min 1 h after the first stimulation to lower the GH baseline, the second response to hGRF was also restored to the level of the first response. Neither SRIF infusion after the first hGRF stimulation nor infusion of SRIF without hGRF caused any rebound increase in GH release after cessation of the perifusion. To determine whether SRIF exerts a direct action on the GH response, a prestimulatory perifusion with SRIF (0.1 microM) for 50 min was performed. The treatment tended to facilitate the pituitary response to hGRF. When 50-min pretreatment with SRIF at a lower concentration (0.05 microM) was given, a significantly facilitated response to the first hGRF stimulation (0.05 microM) was observed. These results suggest that 1) SRIF perifusion rapidly restores the attenuated response to a second hGRF challenge by lowering GH release to basal levels; and 2) SRIF pretreatment facilitates the GH response to the first hGRF challenge.