Previous work has shown that the intradentate administration of colchicine produces time-dependent behavioral and neurochemical changes. Deficits in learning and memory and alterations in the signal transduction process for the cholinergic muscarinic receptor have been observed up to 12 weeks after colchicine treatment. To study the long-term effects of colchicine administration on cognitive function and the cholinergic system, 6 month-old male, Fischer-344 rats were injected with 2.5 microgram of colchicine bilaterally in the dorsal and ventral hippocampus. Twelve months later the animals were tested for the acquisition of a spatial reference memory task in the Morris water maze for 8 days, with 4 trials of 60 seconds each day. At the completion of the behavioral testing, one half of the rats were used for histochemical studies. A significant deficit in acquisition in the water maze was observed in animals 1 year after colchicine administration. Neurochemical studies showed an increase in carbachol-induced PI metabolism in the rat hippocampus 1 year post-lesion with colchicine.