This study describes a technique for the direct daily measurement of arterial blood pressure, sampling of arterial blood, and continuous intravenous infusion in free-moving, conscious, Swiss-Webster mice. Catheters were chronically implanted in the femoral artery and vein, tunneled subcutaneously, exteriorized at the back of the neck in a lightweight tethering spring, and attached to a swivel device at the top of the cage. Time-control experiments (n = 8) demonstrated stable values of mean arterial pressure (MAP, 116 ± 1 mmHg) and heart rate (HR, 627 ± 21 beats/min) for up to 35 days after catheter implantation. It was further observed that restraining mice (n = 7) increased MAP by 10 ± 3 mmHg and HR by 78 ± 8 beats/min from the values observed under free-moving conditions. To demonstrate the chronic use of the venous catheter, intravenous infusion ofN ^G-nitro-l-arginine methyl ester (l-NAME, 8.6 mg ⋅ kg⁻¹ ⋅ day⁻¹,n = 6) for 5 days significantly increased MAP from 117 ± 4 to 131 ± 4 mmHg without altering HR. In a final group of mice (n = 5), orall-arginine (2% in drinking water) increased plasma arginine concentration from 90 ± 7 to 131 ± 17 μM and preventedl-NAME hypertension. These experiments illustrate the feasibility of long-term intravenous infusion, direct arterial blood pressure measurements, and arterial blood sampling in conscious mice.