Injury of an arterial wall results in the growth of a neointima which can cause significant luminal narrowing. Current theories do not adequately explain the experimental and clinical data. We propose the hypothesis that some substance produced by the media is inhibitory to smooth muscle cell proliferation. This substance cannot cross the normal intima. Following an injury which removes the intima this substance quickly diffuses out of the arterial wall into the blood, its concentration in the arterial wall falls and proliferation of smooth muscle cells begins. Later, as the arterial wall volume increases and the lumen (and, thus, area for diffusion) decreases, the substance returns to inhibitory levels and intimal hyperplasia ceases.