The effect on normal brain of continuous interstitial laser irradiation at 630 nm through an implanted cylindrical-shape, diffusion-tipped optical fiber was studied in the rat. Brain water content in the laser irradiation area (LIA) and Evans blue (EB) dye content in selected areas of the brain were measured for different laser power outputs from 0 to 250 mW after 5 minutes of photoradiation. The degree and nature of tissue damage was examined histologically and correlated with the laser power level. There is significant brain damage, blood brain barrier (BBB) disruption, and brain edema in LIA for laser power outputs in excess of 100 mW from the diffusion tip (p less than 0.001). Brain edema in the LIA is strongly correlated with BBB disruption indicated by the presence of EB. Histologically, the cortical surface was more susceptible than deeper white matter regions to interstitial laser irradiation. Possible indirect mechanisms of brain injury from interstitial laser irradiation are discussed.