Combining the centrally acting drug yohimbine with the peripheral conditioner sildenafil might be an approach to erectile dysfunction cases in which sildenafil alone failed. This work aimed to investigate the effect of yohimbine on sildenafil-induced facilitation of erectile process. Erectile responses to electrical stimulation of the cavernous nerve in anesthetized male rats were recorded. Intracavernosal pressure/systemic arterial pressure (ICP/SAP) was calculated, 1 and 5 min after intravenous administration of sildenafil, yohimbine or a combination of both. Changes in sexual arousal and copulatory performance indices were compared before and after these injections using behavioral mating experiments. It was shown that systemic administration of sildenafil produced a significant increase in ICP/SAP than control at doses >or=10 micromol kg(-1). Yohimbine alone failed to potentiate erectile responses but yohimbine (1 micromol kg(-1)) significantly potentiated the effect of sildenafil 1-10 micromol kg(-1) and 1 mmol kg(-1), 1 and 5 min after injection. Potentiation of ICP/SAP induced by their combination was greater than the sum of the effects of the corresponding doses of either drug at the same time interval. A nonsignificant additional decrease in SAP than sildenafil-induced was observed if administered with yohimbine. Addition of sildenafil to yohimbine significantly enhanced the effect of the latter on intromission frequency, intercopulatory interval and the number of ejaculations per session. It is concluded that yohimbine may enhance and prolong the effect of sildenafil on erectile process without additional hypotension. Sildenafil may enhance the central effects of yohimbine on erection; it amplifies the effect of yohimbine on male copulatory performance but not on sexual motivation. The potential beneficial effect of the combination was found to be more pronounced on the central component than on the peripheral component of the erectile process.