After a 0100-0300 h nadir, the insulin requirements to maintain blood glucose at 90-110 mg/dl increase substantially in the prebreakfast (0600-0800 h) period in some insulin-dependent diabetic patients (IDDMs). Early insulin-like and delayed insulin-antagonistic effects of physiologic early morning increases in growth hormone (hGH) secretion may account for this variability of overnight insulin requirements. To assess the role of hGH, we studied five IDDMs using a closed-loop insulin infusion device (Biostator, GCIIS). Either saline (C) or somatostatin plus glucagon (SRIF + G) was infused during separate overnight (2400-0800 h) study periods. An infusion of hGH from 2400 to 0130 h was added to SRIF + G infusion during an additional study period (SRIF + G + hGH). In comparison to 0100-0300 h, mean insulin infusion rates required to maintain blood glucose values between 105 and 120 mg/dl during the prebreakfast period increased by 66 ± 25% during C, and 42 ± 12% during SRIF + G when serum growth hormone was suppressed to ≤ 0.75 ng/ml. During SRIF + G + hGH, the mean prebreakfast insulin infusion rate increased by 42 ± 11% with a mean peak hGH level of 14.7 ± 5.4 ng/ml at 0130 h. Mean plasma free insulin levels remained constant during the night despite the significantly higher insulin infusion rates between 0600 and 0800 h. During SRIF + G, insulin requirements remained constant overnight before 0600 h, whereas during both C and SRIF + G + hGH conditions, a nadir was noted between 0100 and 0300 h. Data pooled from 10 overnight, saline infusion studies suggest that the early morning nadir in insulin requirements occurs within 60 min of the peak hGH concentration. We conclude that the physiologic early morning increase in hGH is not an essential component of the prebreakfast increase in insulin requirements. Nocturnal growth hormone secretion may, however, contribute to the early morning nadir in insulin requirements seen in IDDM.