We evaluated the efficacy of 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUR) as anticontractile agents in an in vitro model that measures the ability of human and rabbit fibroblasts to contract a collagen gel. Human fibroblasts were more contractile than rabbit fibroblasts, required higher concentrations of 5-FUR for inhibition of contraction, and were able to tolerate higher doses of the drug. 5-FU failed to inhibit contraction of human fibroblasts at concentrations up to 1.5 mM (200 micrograms ml-1), but significantly inhibited rabbit fibroblast contraction, although to a lesser degree than 5-FUR under similar conditions. 5-Fluorouridine (100 microM, 26 micrograms ml-1) inhibited contraction of human fibroblasts by more than 80%, whereas only 10 microM (2.6 micrograms ml-1) 5-FUR was required for 90% inhibition of rabbit fibroblast contraction. 5-FUR was cytotoxic to rabbit fibroblasts at concentrations of 200 microM (52 micrograms ml-1) or greater, but 800 microM was non-toxic to human fibroblasts after 96 hr exposure. At concentrations of 1.5 mM, 5-FU had no significant effects on the viability of either human or rabbit fibroblasts. These results suggest that 5-FUR may prove useful for the treatment of human ocular proliferative disorders in which contraction of fibrocellular elements is thought to play a part. They also suggest that fluoropyrimidine dosages found to be effective in a rabbit model of proliferative vitreoretinopathy may be less effective in humans and that 5-FUR levels shown to be toxic to rabbit-derived cells may be tolerated by humans cells.