Daunomycin is a potent antiproliferative agent which has been shown to prevent experimental proliferative vitreoretinopathy. However, toxic effects on the rabbit retina have been reported even for the lowest effective doses. In a previous report we demonstrated that subdivided doses rather than single doses of daunomycin improves the efficacy in prevention of experimental proliferative vitreoretinopathy. To evaluate whether dose subdivision would also have an alleviating effect on drug toxicity, we administered 15 nmol daunomycin in doses of 10 nmol and 5 nmol 4 h apart into the vitreous cavity of rabbit eyes which had previously undergone vitreous gas compression. All contralateral eyes received sham treatment. Simultaneous electroretinographic recordings from both eyes on days 0, 3, 7, and 14 demonstrated a significant b-wave decline in drug-exposed eyes. Morphological studies on these eyes revealed no retinal damage. Our findings suggest that dose subdivision does not eliminate the retinal toxicity of daunomycin.