Treatment with insulin-like growth factor I (IGF-I) is accompanied by mild generalized and reversible edema. These changes may be due to increased capillary permeability. Therefore, we studied the effects of subcutaneous IGF-I treatment in healthy subjects on capillary permeability of the skin and the retina. Eight healthy subjects were treated with saline or recombinant human IGF-I (rhIGF-I) (10 micrograms.kg-1.h-1 s.c.) in a randomized crossover fashion. Transcapillary diffusion of sodium fluorescein (NaF) was quantitated by video densitometry in the skin in all subjects on the 4th treatment day. In seven subjects, plasma penetration of NaF at the blood-retinal barrier was investigated using vitreous fluorometry (VF) on days 3 and 5. Fluorescent light intensities of the skin and plasma penetration determined by VF were significantly higher during the IGF-I treatment as compared with those during the control situation. In conclusion, IGF-I treatment at the above dose is accompanied by increased transcapillary diffusion of NaF in skin and in retinal vessels.