Massage over the site of a subcutaneous insulin injection markedly enhances the absorption of insulin. To investigate whether this reflects an increased dispersion of insulin in the tissue, the area of distribution of radioactivity at 125I-insulin (10 U) injection sites in thigh was determined in eight healthy volunteers by external scanning on a day with standardized massage and on a control day. Insulin absorption (first order disappearance rate constants and appearance of serum immunoreactive insulin, IRI) and plasma glucose were determined concomitantly. The area of distribution of 125I increased 30 +/- 15% (p less than 0.05) on the massage day, which was not significantly different from the change during control (12 +/- 10%). The rate constants for 125I-insulin increased markedly (237 +/- 74%) on the massage day and much less (49 +/- 15%) on the control day (p less than 0.01). Peak IRI levels were 49 +/- 8 mU/l on the massage day and 17 +/- 2 mU/l on the control day (p less than 0.01). The glucose lowering effect was also more pronounced on the massage day. These results indicate that the marked enhancement of insulin absorption induced by massage of the injection site is not directly related to expansion of the insulin depot in the subcutaneous tissue.