Hematocrit (H) levels can change during hemodialysis, and these changes in H are inversely related to changes in blood volume (BV). The objectives of this study were to determine whether mean arterial pressure (MAP) decreases with decreasing BV and rising H during hemodialysis, and to determine the relationship between dialysis induced intravascular volume depletion and intradialytic morbid events (IME), defined as hypotension, cramping, or lightheadedness that led to dialysis staff intervention. We monitored H continuously using a noninvasive optical technique in 93 hemodialysis sessions in 16 patients. IME occurred in 48 sessions. MAP decreased with increasing H in 10 of 16 patients (P < 0.05), but the relationship between MAP and H varied among the patients. The rate of BV change during sessions without morbidity (5.6 +/- 3.6 [SD] %/hr) was lower (P < 0.001) than that preceding IME in the other sessions (12.2 +/- 5.5 [SD] %/hr). Twelve of 16 patients who exhibited recurrent IME during this study experienced these events when H reached a patient specific threshold. It is concluded that MAP decreases with decreasing BV and increasing H in many patients on hemodialysis, and that a high rate of BV change often indicates that IME are forthcoming. It is further hypothesized that a patient specific H threshold is indicative of a critical BV level below which certain patients experience IME.