Chlorpropamide, an oral hypoglycemic agent, was tested for effects on excision repair and postreplication repair of ultraviolet (UV) damage of DNA in CHO-K1 cells. The technique used to measure excision repair involved isopycnic centrifugation of density- and isotopically-labeled DNA. Alkaline sucrose gradient sedimentation was used to monitor postreplication repair. Administration of chlorpropamide at 250 and 1000 microgram/ml after exposure of cultures to 254-nm UV reduced excision repair to 79 and 67%, resp., of control. Post-irradiation treatment with the drug at 1000 microgram/ml inhibited the postreplication gap-filling mechanism almost as effectively as did 2 mM caffeine. The hypoglycemic agent was also found to reduce UV cell survival but did not appear to alter the rate of semiconservative replication. These results suggest that chlorpropamide inhibition of repair processes may potentiate the effects of known mutagenic hazards and may also be responsible for the increased incidence of chromosome aberrations in patients treated with the drug.