In this double blind randomized study we compared the insulinkinetic, insulindynamic and the frequency of hypoglycemic events after s.c. injection of human insulin and the insulin analogue (B28Asp). Fourteen c-peptide negative patients treated with continuous subcutaneous insulin infusion (CSII) were included in the study. Their mean age was 42.9 (range 26-60 yrs), duration of diabetes 18.5 (5-29) and mean duration of CSII 6.3 yrs (3-10). Serum free insulin (FIRI) was determined from 8:00 to 11:00 h, and blood glucose from 7:00 to midnight. Maximum FIRI values were obtained after 45 min for (B28Asp) and after 90 min for Actrapid HM. Maximum blood glucose increase (Tmax) was obtained 60 min after injection of (B28Asp) and 90 min after Actrapid HM. The AUCBC was greater after administration of Actrapid HM compared to (B28Asp) (p < or = 0.05). A total number of 16 hypoglycemias (BG < or = 3.3 mmol.l-1) were registered. 8 episodes were induced equally by (B28Asp) and by Actrapid HM. We conclude that in insulin dependent diabetic patients the insulin analogue (B28Asp) showed a faster absorption and less hyperinsulinemia than Actrapid HM after s.c. administration. The corresponding BG-values were higher after s.c. administration of Actrapid HM compared to (B28Asp). These findings in patients support the concept of a more physiological effect of rapid acting insulin analogues than of regular insulin.