Clinical factors which might influence the absorption of subcutaneously injected 125I-NPH insulin were studied in 101 diabetics. The disappearance curve was monoexponential after a delay period of 1.5±0.8 h (mean ± SD). Lipohypertrophy significantly prolonged insulin absorption (half life (T1/2) = 11.2±3.1 h, p = 0.0001) . Low bicarbonate levels increased the absorption (T1/2 3.9±2.3 h, p< 0.05). Lean diabetics had a faster absorption (6.2 ± 1.9 h) than normal weight diabetics (7.5 ± 2.0 h, p< 0.02). Sex, age, diabetes duration and injection depth did not influence T1/2. The half life was significantly inversely correlated to the resting subcutaneous blood flow (r= -0.882, p< 0.01). The overall interindividual coefficient of variation for insulin absorption in nonketotic diabetics was 27.4%. Also considerable intrapatient day-to-day variation was found (24.5%), and between different injection sites (30.2%). These variations emphasize the drawbacks of conventional insulin therapy in the management of insulin-requiring diabetics.