Effects of chronic ethanol exposure on the synapse-to-neuron ratio of rat locus ceruleus were investigated. Male Sprague-Dawley rats were given an ethanol-containing liquid diet for 4 months starting at an age of 5 weeks. Littermates, given isocaloric amounts of an ethanol-free diet, served as control. The animals were perfusion fixed using a mixture of glutaraldehyde and paraformaldehyde. Synapse-to-neuron ratio was estimated by the double disector method and calculated from (N(s)/A) x (N(sec) -1) / (N(n)/A) where N(s)/A is the number of synapses per unit area estimated in a disector with a height of one section and N(sec) -1 is height of the disector, i.e., the number of sections, used for estimating the number of neurons per area (N(n)/A). The mean estimated synapse-to-neuron ratio was 2046 +/- 544 (SD) in ethanol-fed rats and 4291 +/- 1171 (SD) in control rats. The difference is statistically significant (p < 0.05). The finding may be of relevance for understanding the development of abuse, tolerance, drug dependence, and abstinence reactions.