Mice were injected once daily for 13 days with (+/-)-DOI ((+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and the induced head-twitch response (HTR) was scored. On days 2-5 HTR was reduced to less than 50% of day 1, and then returned to control levels by day 13. Challenge doses of (+/-)-DOI administered on days 15, 17 or 19 elicited significantly exaggerated responses. Thus, chronic treatment with (+/-)-DOI may cause an initial down-regulation followed by an up-regulation of 5-HT2 receptor function after cessation of such treatment.