Nine insulin-dependent diabetics with undetectable plasma C-peptide (less than 0.05 nmol l-1) and without insulin antibodies (insulin binding to IgG less than 0.05 Ul-1) received subcutaneous injections of 10 U 125I-labelled soluble human or porcine insulin in the thigh on 2 consecutive days. Disappearance rates of 125I were monitored continuously by external counting and plasma insulin levels were determined during rest for 30 min, bicycle exercise of moderate intensity for 40 min, and 60 min recovery. Subcutaneous blood flow was measured concomitantly in the contralateral thigh by the 133Xenon clearance technique. During the initial period of rest human insulin was absorbed approximately 40% faster than its porcine analogue (first order rate constants 0.37 +/- 0.06 vs 0.27 +/- 0.06% min-1, P less than 0.05) and the increment of the area under the plasma insulin curve was greater after human than after porcine insulin (184 +/- 46 vs 112 +/- 42 mUl-1 min, P less than 0.05). Exercise enhanced the absorption rates for both 125I-insulins to 0.50 +/- 0.06 and 0.48 +/- 0.10% min-1 for human and porcine insulin, respectively (P less than 0.05). This increase was less pronounced for human compared to porcine insulin (49 +/- 19 vs 105 +/- 40%, P = 0.06). During exercise plasma insulin rose to 37 +/- 5 mUl-1 after human and 30 +/- 5 mUl-1 after porcine insulin and the areas under the plasma insulin curves were similar. During the recovery phase the absorption rates decreased slightly compared to the exercise value for both insulins. The blood glucose lowering effect was similar for the two insulins.(ABSTRACT TRUNCATED AT 250 WORDS)