Terazosin is a quinazoline antihypertensive agent that is chemically similar to prazosin. The saturated furan ring of terazosin distinguishes these two compounds. Terazosin (0.1 to 3.0 mg/kg) lowered blood pressure without increasing heart rate when given orally to spontaneously hypertensive rats. No tolerance was observed during five days of repeated oral administration. Although equally efficacious in spontaneously hypertensive rats as its congener prazosin, terazosin exhibited a more gradual onset of action than prazosin, a more uniform and linear dose-response curve, and a less variable duration of action. When administered intravenously to dogs, terazosin lowered blood pressure primarily by decreasing peripheral vascular resistance. Pretreatment with phenoxybenzamine but not with atropine or propranolol resulted in a greatly reduced hypotensive response to terazosin, demonstrating that this effect of terazosin is mediated by a sympatholytic mechanism of the alpha type. The nature of the alpha-blocking properties of terazosin was evaluated in vitro using both radioligand binding studies and functional tests in rabbit aorta and pulmonary artery. These studies demonstrated that terazosin is highly selective for alpha1 receptors. The affinity for alpha1 receptors was approximately one-third that of prazosin. Like prazosin, terazosin displayed minimal interaction with alpha2 receptors. Median lethal dose values in rats ranged from 0.255 to 0.270 g/kg for intravenous administration and from 5.5 to 6.0 g/kg, for oral administration. Oral administration of high doses of the compound to rats did not produce any gastrointestinal irritation and/or apparent abnormal behavioral effects. Comparison of the oral activity of terazosin in spontaneously hypertensive rats with the oral toxicity values in normal rats revealed a high efficacy/safety ratio. Terazosin given intravenously to rats and mice was 2.6 to 5.0 times less toxic than prazosin. The absorption of terazosin appeared to be slower than that of prazosin in rats. However, from eight to 16 hours after dosing, terazosin concentrations in plasma exceeded those of prazosin, suggesting the possibility of once-daily dosing with terazosin. In addition, terazosin exhibited statistically significant cholesterol lowering effects in gerbils.