Absorption of pulsed laser radiation by individual melanosomes produces located heating and microactivation bubble formation around the particles, with transient bubble lifetimes of a few hundred nanoseconds. Intracellular cavitation in the retinal pigment epithelium (RPE) leads to prompt cell death. Threshold laser fluence for cavitation bubble formation and RPE cell damage was measured as the exposure spot size was varied from 20 to 200 micrometers using a RPE tissue explant model. The threshold energy for cell killing decreased with decreasing spot diameter but the fluence was nearly constant for all spotsizes. How this compares with data from in vivo animal studies is discussed.