Blood glucose (BG) was monitored continuously and plasma growth hormone (hGH) was determined at hourly intervals in patients under standardized ambulatory-fed conditions (48-hr study periods after prolonged preparation for optimal therapy). BG regulatory stability was quantified on the basis of mean amplitude of glycemic excursions (MAGE, a measure of withinday BG variability), mean of daily differences of matched BG values on successive days (MODD, a measure of between-day BG variability), and mean BG (MBG, a measure of diurnal glycemia). Eight unstable diabetics, all with high BG parameters, also had high mean hourly hGH and peak hGH values compared with three stable diabetics and three normal subjects. While inadvertent hypoglycemic episodes and rcise-related and sleep-related hGH increases contributed to the higher hGH levels in the unstable diabetics, none of these events accounted for the observed differences. In this study, diabetic instability and sex were found to exert significant effects. At the time of hGH increases, BG concentrations were consistently higher in diabetics than in normals. A lower mean glycemia in unstable diabetics (during intensified therapy with 4 daily injections of short-acting insulin, compared with 1 or 2 daily injections of intermediate-acting insulin) did not lower the mean level of hourly hGH values nor the mean height of the hGH peaks. However, the MAGE and MODD values also were not decreased by such intensified insulin therapy. Higher than normal diurnal hGH levels exist in unstable diabetics even under apparently optimal therapeutic conditions