Canine nasal mucosa was studied in vitro to examine (1) the production of vasoconstriction by cocaine and, (2) the epithelial permeability of cocaine. Cocaine, by itself, failed to induce any contraction of the nasal blood vessels but did enhance contractions resulting from electrical stimulation or addition of norepinephrine. Results indicate that cocaine produces vasoconstriction by blocking the reuptake of endogenous norepinephrine rather than any direct action on vascular smooth muscle. Cocaine was found to be three times more permeable than sucrose, which has a similar molecular weight. The transepithelial permeability of cocaine was independent of direction and did not display competition. Results indicate that cocaine permeates by simple diffusion and that the relatively high permeability is due to a greater lipid solubility. Cocaine was found to accumulate in the nasal mucosa. A significant portion of the accumulation is associated with specific sites that are characteristic of catecholamine uptake sites.