Two dimensional diffusion of macromolecules through the interstitial in the hamster cheek pouch was studied with intravital fluorescence microscopy. After topical application of Bradykinin, the movement of Fluorescein isothiocyanate (FITC)-labeled dextrans of average molecular weight 150,000 daltons (Dextran 150) was recorded on videotape which latter was played back frame-by-frame for analysis by digital image processing. Leakage of macromolecules in response to topical application of Bradykinin occurs at discrete leakage site in post caplillary venules of 15-25 um diameter, rather than in the capillary themselves. A mathematical model of two dimensional convection plus diffusion was used to simulate the macromolecule transport. The model simulations were compared with the experimental data to estimate interstitial diffusion coefficients and velocities. The model which best fit the experimental data consisted of four discrete leakage points at the origin. The additional of a small interstitial convective component in both the x and y directions gave a better fit of data than did a pure diffusion model. The apparent diffusion coefficient of FITC-dextran 150 was estimated to be 1.0x10-7 cm2/sec. The interstitial velocities on the X- and Y- axes were both the same and estimetal as 1.0x10-4 cm/sec for the best fit in the interstitial diffusion space of the hamster cheek pouch