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1. An isolated gastrocnemius muscle from cat was perfused with a modified Ringer fluid containing the extracellular tracers mannitol, sucrose and inulin and in some cases tritiated water (HTO). When equilibration of the tracers between the perfusate and the tissue was obtained, perfusion with tracer-free fluid was started.

2. The fractional rate of escape, (t), of the tracers was followed. For all tracers it declined steadily with time. The rate of decline was faster for the smaller extracellular molecules when any combination of two extracellular tracers was studied.

3. Arrest of flow for 1-2 min lead to an increase in (t) for the extracellular tracers when flow was resumed. There was little or no effect upon (t) for HTO.

4. Doubling the rate of flow had no effect upon (t) for the extracellular tracers, while that of HTO increased.

5. We conclude that the cause of the decline in (t) for the extracellular tracers is concentration gradients in the interstitial space. The findings raise problems in methods for studying capillary permeability by means of the fractional rate of escape of tracers from the interstitial space into the vascular system.