Objective: Sildenafil citrate is a commonly used drug for the treatment of erectile dysfunction accompanied with fluoxetine HCl treatment. Fluoxitine HCl inhibits the cytochrome P450 CYP3A4 and CYP2C enzymes which are the main metabolizing isozymes of sildenafil citrate. Since sildenafil citrate, activating mainly NO pathway, can cause vasodilation and hypotension. The prolonged metabolisation of this compound may aggravate the severity of hypotension. In the present study, cardiovascular changes upon sildenafil citrate administration alone and after fluoxitine HCl treatment for two months were investigated in anesthetized male Sprague-Dawley rats. Material and Methods: A single dose of sildenafil citrate was administered i.p. into control (n= 18) and two mounths of fluoxetine HCl (0.285 mg/kg/day) treated experimental (n= 18) group rats. The operated rats were monitored to record the changes of systolic, diastolic, mean and pulse pressures and heart rate for six hours under ketamine and xylazine induced anesthesia. Results: Our results indicate that there was a gradual and significant decrease in blood pressure by the time within the groups (ranging from 93.8 ±4.9 mmHg basal MAP to 56.0 ± 7.9 mmHg of 360 minute MAP value in control and from 88.5 ± 7.6 mmHg to 52.2 ± 14.0 mmHg for experimental group). But decrease pattern in blood pressure was not significantly different between the groups. No statistical differences were found between control and experimental groups for each cardiovascular parameter. Conclusion: In conclusion, sildenafil citrate injection caused a gradual hypotension, and there was no significant additive effect on the hypotension and other examined cardiovascular parameters at 0.357 mg/kg dose in the subchronically fluoxetine HCl treated male rats. However when the higher doses of sildenafil was treated, it has interacted with anesthesia and all the animals have died. Copyright © 2005 by Türkiye Klinikleri.