A model of UV-induced DNA damage in oceanic bacterioplankton was developed and tested against previously published and novel measurements of cyclobutane pyrimidine dimers (CPD) in surface layers of the ocean. The model describes the effects of solar irradiance, wind-forced mixing of bacterioplankton and optical properties of the water on net DNA damage in the water column. The biological part includes the induction of CPD by UV radiation and repair of this damage through photoreactivation and excision. The modeled damage is compared with measured variability of CPD in the ocean: diel variation in natural bacterioplankton communities at the surface and in vertical profiles under different wind conditions (net damage as influenced by repair and mixing); in situ incubation of natural assemblages of bacterioplankton (damage and repair, no mixing); and in situ incubation of DNA solutions (no repair, no mixing). The model predictions are generally consistent with the measurements, showing similar patterns with depth, time and wind speed. A sensitivity analysis assesses the effect on net DNA damage of varying ozone thickness, colored dissolved organic matter concentration, chlorophyll concentration, wind speed and mixed layer depth. Ozone thickness and mixed layer depth are the most important factors affecting net DNA damage in the mixed layer. From the model, the total amplification factor (TAF; a relative measure of the increase of damage associated with a decrease in ozone thickness) for net DNA damage in the euphotic zone is 1.7, as compared with 2.1–2.2 for irradiance weighted for damage to DNA at the surface.