Capillary permeability of 131I-albumin in skeletal muscle was determined by applying the "single injection, residue detection" method to the autoperfused cat gastrocnemius muscle preparation. Experiments at zero venous pressure gave an average capillary extraction fraction, E, of 0.028 at a plasma flow of about 3 ml X (100 g)-1 X min-1. The permeability-surface area product, PS, was on average 0.075 ml X (100 g)-1 X min-1. Experiments at a venous pressure of 10 mm Hg gave essentially the same PS product (0.070 ml X (100 g)-1 X min-1. Further experiments demonstrated that stagnant intravascular pools of 131I-albumin were not present. The free diffusion coefficient in water at 37 degrees of the purified 131I-albumin was 0.0631 X 10-5 cm2 X sec-1). The distribution volume for 131I-albumin in the interstitial space was 3.5 ml X (100 g)-1 X sec-1. Assuming a capillary surface area of 70 cm2 X g-1 the permeability coefficient was calculated to be 18 X 10(-8) cm X sec-1 which is about 3 to 10 times higher than values obtained by lymph sampling methods. The results indicate that the predominant transcapillary transport mechanism for 131I-albumin is diffusion. When analyzed according to the theory of restricted diffusion the results are compatible with transcapillary diffusion through pores with an effective equivalent pore radius of 145 A.