The effects of intrapulmonary insulin administration in non-insulin-dependent diabetes mellitus (NIDDM) were studied in 12 patients in a double-blind randomized placebo-controlled intervention study. Regular human insulin, 100 U ml-1, was given as an aerosol by oral inhalation after a 12-h fasting. A significant decrease in blood glucose concentration, from 10.2 +/- 0.5 to 6.1 +/- 0.5 mmol l-1 (p < 0.0001) and a significant rise in serum insulin concentration, from 11.2 +/- 1.8 to 28.0 +/- 2.6 mU ml-1 (p < 0.0001), was seen. Serum C-peptide levels decreased from 1.6 +/- 0.2 to 1.0 +/- 0.1 nmol l-1 (p < 0.0001). No side-effects were reported following aerosol inhalation. If similar results can be obtained when using this route for insulin administration to insulin-dependent diabetes mellitus patients, this may be a useful complement to traditional subcutaneous insulin injections in these patients.