Data obtained during 46 inadvertent hypoglycemic episodes in 8 severe diabetics under standardized, near-normal activities (ambulatory and fed) were compared with data obtained during 9 insulin infusion tests in 7 of the same diabetics. Blood glucose (BG) was continuously monitored, urinary glucose and ketone body excretions were determined, and plasma growth hormone (HGH) was assayed (the latter in intermittently obtained specimens). During comparable BG changes and at comparable BG levels, HGH increased in 78% of episodes and 67% of tests. HGH increases during episodes were lower (p <0.01) and started at higher BG levels than during tests. No consequences of HGH increase on post-hypoglycemic BG or urinary glucose and ketone body excretion could be discerned. Clinical manifestations of hypoglycemia were present in 63 % of all episodes. HGH increased in 93 % of such symptomatic episodes. BG changes and levels and HGH increases (when they occurred) were similar in symptomatic and asymptomatic episodes. However, 79% of episodes with HGH increase were symptomatic and 83% of episodes without HGH increase were asymptomatic. Insulin infusion tests were uniformly symptomatic but, in 1/3 of the diabetics, no HGH increase occurred during hypoglycemia. During constant dietary intake and attempts at accurate diabetic regulation of ambulatory, fed, insulin-dependent, severely diabetic patients, BG changes do not exert dominant control over HGH release, and HGH increases during hypoglycemia do not alter those consequences of hypoglycemia that were measured. Among the phenomena evaluated, the symptomatic stress of hypoglycemia was most consistently related to increase of HGH during hypoglycemic episodes.