We have developed a new assay which allows us to monitor the rates of repair of potentially lethal damage in u.v. (254 nm)-irradiated normal human skin fibroblasts. Using this assay we have shown that, in non-dividing cells, the majority of biologically effective excision repair is completed within 4 h following irradiation with low fluences of u.v. (1.5-6.0 J/m2). During this time, non-dividing cells removed only approximately 20% of the pyrimidine dimers induced in DNA by a u.v. fluence of 3.0 J/m2 as measured by the loss of u.v.-endonuclease-sensitive sites under identical repair conditions. The rates of repair of potentially lethal damage were also found to be independent of u.v. fluence over the range 1.5-6.0 J/m2 in non-dividing cells. In contrast, in cells irradiated in exponential growth with 1.5 J/m2, the rate of biologically effective repair was comparable with that observed in non-dividing cells but the efficiency of the repair process declined progressively with increase in u.v. fluence from 1.5 to 6.0 J/m2. Our data support the concept that the biological recovery of u.v.-irradiated cells depends on the preferential repair of damage in functionally important domains in the genome.