Interleukin-6 (IL-6) has been implicated as a contributing factor in the pathogenesis of hypertension, although the mechanisms involved are unclear. Studies conducted in vitro suggest that IL-6 may have a direct effect on vascular tone and may modulate constrictor responses to agonists. Whether this effect can be observed in vivo is unknown. Therefore mice were treated with either IL-6 (16 ng/h, s.c.) or vehicle for 14 days and the acute blood pressure and heart rate responses to endothelin-1 (ET-1), angiotensin II (AngII) and phenylephrine (PE) were assessed under isoflurane anesthesia. Blood pressure responses to ET-1 were identical in vehicle- and IL-6-infused mice, both in the presence and absence of ganglion blockade with chlorisondamine. The fall in heart rate during ET-1 responses was significantly attenuated in IL-6-infused mice with autonomic reflexes intact (vehicle versus IL-6, P < 0.05 at 1 and 3 nmol/kg of ET-1), but this difference was not observed following ganglionic blockade. Both blood pressure and heart rate responses to AngII were indistinguishable between IL-6- and vehicle-infused mice, as were responses to PE except for a significant increase in the blood pressure response and decrease in the heart rate response in IL-6-infused mice observed only at the highest dose of PE (300 µg/kg, P < 0.05). These findings show that despite what might be predicted from studies conducted in vitro, chronic exposure to elevated plasma IL-6 concentrations in itself does not predispose the mouse to enhanced responsiveness to vasoconstrictors in vivo.