Male, Fischer-344 rats received bilateral injections of colchicine (2.0 micrograms/site) into the dorsal and ventral hippocampus to destroy dentate gyrus granule cells. Colchicine impaired the ability of rats to learn a brightness discrimination, active avoidance task in a Y-maze. Acquisition was measured in 120-trial sessions given once weekly for 3 or 4 weeks. In a second experiment, colchicine-treated rats were tested in a modified procedure in which only the tone warning stimulus and a light directional cue were presented; shock was not presented. Colchicine-treated rats showed an enhanced response bias under these conditions, selecting to go to the unlighted arm with a greater frequency than the control rats whenever the tone and light were activated. These data are consistent with other reports indicating that rats with hippocampal lesions are impaired in the acquisition of a simultaneous discrimination if a response bias exists to one of the choices.