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The heating and restraint inherent to tail-cuff measurement of systolic blood pressure (SBP) in rats may alter SBP and introduce a 'biological' error in its estimation by this technique. This problem was examined in unanesthetized normotensive and hypertensive rats fitted with an arterial catheter. All SBP values recorded in unrestrained rats during a 2 h period were averaged by computer and compared with intra-arterial SBP measurements observed white the rat was being subjected to the tail-cuff procedure. With the latter procedure, SBP was 16 ± 2mmHg lower in normotensive rats (P<0.01) and 7 ± 3 mmHg higher in hypertensive rats (P<0.05) than when the rats were unrestrained. The effects of heat and restraint, both separately and in combination, on SBP were evaluated during four additional 30-min monitoring periods. In both groups of rats, restraint failed to alter SBP and heat lowered it slightly. The two stimuli, combined, lowered SBP in normotensive rats, but raised it by 12 ± 2 mmHg in hypertensive rats (P<0.01). Thus, tail-cuff SBP measurements represent under- and overestimates in normotensive and hypertensive rats, respectively, since the two groups respond to the procedure in opposite manners.