We have validated a noninvasive computerized tail-cuff system for measuring blood pressure in mice. The system was designed to perform all functions automatically, including a programmable routine of cuff inflation and deflation, analysis and assignment of pulse rate and blood pressure, and recording of data electronically. To evaluate this system over a range of blood pressures, we gave groups of mice enalapril or N^G-nitro-l-arginine methyl ester in their drinking water. For each of these groups, an equal number of control mice were given nothing in their drinking water. Tail-cuff blood pressures were recorded as the means of blood pressures determined on at least 3 days after at least 7 days of training. Tail-cuff enalapril and control group means were measured both 3 and 4 months after enalapril (or no drug) was begun; the group means at 3 months were not significantly different from the group means at 4 months. These results demonstrate that the system gives reproducible results. After the tail-cuff measurements were completed, intra-arterial blood pressures were attempted in all mice under unrestrained, unanesthetized conditions, and individual mouse (n=22) blood pressures with the use of the two methods were compared. The blood pressures from individual mice by tail-cuff and intra-arterial methods were highly correlated (r=.86, P<.01). The means for the four mouse groups were also highly correlated (r=.98, P<.02). These data show that blood pressures measured on trained mice by a computerized noninvasive tail-cuff system are reproducible and correlate well with intra-arterial blood pressures measured on unrestrained, unanesthetized mice.