Blood intermediary metabolite and hormone concentrations have been assessed in 10 insulin-dependent diabetic patients on SC injection therapy and during 24 hr of relative normoglycaemia on an artificial pancreas (GCIIS). Mean blood lactate (0.96 +/- 0.07 mmol/l) and pyruvate (0.087 +/- 0.004 mmol/l) levels remained elevated compared to normal controls (0.76 +/- 0.04 and 0.064 +/- 0.003, p less than 0.05 and less than 0.001, respectively). No tendency was detected for these levels to regress towards normal over the 24 hr period on the GCIIS. Mean individual 24 hr blood lactate concentrations correlated significantly with mean free insulin levels (r = 0.85, p less than 0.002), but inversely with prior out-patient diabetic control (r = 0.64, p less than 0.05). The shape of the 24 hr profiles of blood lactate and pyruvate changed between SC therapy and the GCIIS, corresponding in both studies to the form of the free insulin profile. Blood alanine and glycerol profiles were not abnormal on either regime. Blood 3-hydroxybutyrate levels were abnormal on both SC therapy (0.16 1.14 mmol/l) and the GCIIS (0.15 1.20 mmol/l, controls 0.04 1.31 mmol/l), with concentrations on SC therapy correlating positively with previous control. Abnormalities of intermediary metabolite levels persist during feedback normalization of blood glucose levels, with evidence of influences from both prior diabetic control, and current insulin delivery.