The effects of sodium saccharin and caffeine on urinary bladder carcinogenesis in Wistar strain rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Animals were given 0.01% BBN as an initiator for 4 weeks and then sodium saccharin and/or caffeine as promoters for 32 weeks (Experiment I), or were treated simultaneously with 0.001% BBN, sodium saccharin and/or caffeine for 40 weeks (Experiment II). The urinary bladders were then removed and examined by light and electron microscopy. Sequential administration of sodium saccharin after BBN significantly enhanced the induction of hyperplasias compared with administration of BBN alone (Experiment I), and simultaneous administration of sodium saccharin with BBN significantly enhanced the induction of hyperplasia and papillomas compared with BBN alone (Experiment II). Two types of hyperplasias developed in the urinary bladder of rats treated with sodium saccharin alone in both experiments. Caffeine alone had no effect on the rat urinary bladder epithelium, and either sequential or simultaneous administration of caffeine with BBN caused no marked enhancement of carcinogenesis in these experiments.