OBJECTIVE Since the end of the 1980s, the pathological importance of baroreflex function has attracted the attention of many investigators. In our previous studies, it was found that ketanserin lowered blood pressure (BP), decreased BP variability and enhanced baroreflex sensitivity (BRS). The present work was designed to test the hypothesis that the restoration of BRS by ketanserin is not dependent on BP level in conscious rats. METHODS Spontaneously hypertensive rats (SHR) aged 8-12 months were used. Blood pressure was recorded for 60 min and BRS was determined separately before and after intragastric administration of ketanserin, with four doses. In a second experiment, 10-week-old Sprague-Dawley rats were used for preparing a myocardial infarction (MI) model by ligating the coronary artery. MI rats were treated with ketanserin for 5 weeks, with two doses. At the end of the treatment, BP and BRS of the MI rats were studied in conscious state. In addition, the effects of ketanserin on BRS in Sprague-Dawley rats with normal BRS and the effects of prazosin and ritanserin on BRS in SHR were also observed. RESULTS It was found that ketanserin significantly decreased BP and improved BRS in the conscious SHR. The decrease in BP was dose-dependent but the improvement of BRS was not. At the smallest dose (0.3 mg/kg), ketanserin did not lower BP but enhanced BRS. In MI rats, the treatment with ketanserin did not significantly decrease BP, but it improved BRS at both doses administered (0.6 and 10 mg/kg). Ketanserin [3 and 10 mg/kg, intragastric (i.g.)] did not affect BRS in SD rats with normal BRS. Prazosin and ritanserin did not enhance BRS in SHR when administered intravenously. Ritanserin markedly and prazosin slightly enhanced BRS in SHR following intracerebroventricular administration. CONCLUSIONS The restoration of baroreflex function by ketanserin is not BP dependent and this effect is mediated by central 5-HT2A receptor.