Repetitive exposure to short laser pulses is shown to cause selective damage to absorbing structures (cells, organelles, or enzymes) with pulse energies below the threshold energy for single-pulse damage. Directly adjacent structures are spared in vivo. Additivity of (presumably nonphotochemical) subthreshold effects is demonstrated. Selective damage to the retinal pigment epithelium with sparing of the neural retina is shown (514 nm, 5 microseconds, 1-500 pulses at 500 Hz, 2- to 10-microJ pulse energy). A melanin granule model has been developed and applied to the experimental situation. Histological results as well as the basic mechanism for these effects are discussed.