Studies related to 5-HT2A/2C receptors and these receptor-linked phosphoinositide (PI) system in the rat brain during chronic ethanol treatment and withdrawal are discussed. Chronic ethanol treatment (60 days) has no effect on 5-HT2A/2C receptors in the cortex and the hippocampus but significantly decreased 5-HT-stimulated PI hydrolysis in the rat cortex. On the other hand, chronic ethanol treatment (60 days) significantly increased 5-HT2C receptors and 5-HT-stimulated PI hydrolysis in the rat choroid plexus. Ethanol withdrawal (24 h) after chronic ethanol consumption (15 days) results in the down-regulation of 5-HT2A receptors and in a decrease in 5-HT-stimulated PI hydrolysis in the rat cortex. Taken together, these results, along with other reports in the literature, suggest that 5-HT2A/2C receptors or their function are altered during chronic ethanol consumption and withdrawal. Further studies are needed to explore the role of 5-HT2A/2C receptors and the PI signal transduction system in the development of ethanol withdrawal symptoms after chronic ethanol consumption.