Recently, we reported that elevated extracellular potassium concentration in vitro inhibited proliferation and migration of vascular smooth muscle cells, formation of free radical compounds by macrophages, and reduced platelet sensitivity to agonists. In the present study we analyzed the effects of long-term, in vivo elevation of extracellular potassium concentration resulting from changes in dietary potassium intake on the vascular response to injury. The rat carotid artery balloon injury model was employed in 70 adult Sprague Dawley rats assigned to three groups. Beginning 14 days before surgical placement of the carotid lesion and continuing until death, the animals were fed diets containing either low (0.1% potassium, n 25), normal (1.5% potassium, n = 19), or high potassium (4.0% potassium, n = 26). Fourteen days postsurgery the animals were killed and the arteries were analyzed to determine quantitatively the ratio of neointimal to medial area. Dietary potassium had a significant effect on arterial plasma potassium concentration (one-way analysis of variance, P < .01). Group mean and standard errors were 4.26 ± 0.12 mmol/L for the low-potassium group, 5.22 ± 0.19 mmol/L for normal, and 5.80 ± 0.23 mmol/L for the high-intake group. Increases in dietary potassium attenuated neointima formation significantly (P < .05, one-way analysis of variance), with the mean ratio of neointimal area to medial area being 0.447 ± 0.106 for the low-intake animals, 0.384 ± .116 for normal, and 0.240 ± .046 for the high-intake group. These results are consistent with a hypothesis that a high level of potassium intake is effective in inhibiting neointima formation in vivo.