We report two pediatric patients who required blood priming for continuous venovenous hemodiafiltration. Both of these patients developed a significant hypotensive episode with initiation of continuous venovenous hemodiafiltration with immediate resolution on discontinuation. The most notable common characteristics of these patients were the use of the Multi-flo 60 (AN-69) dialyzer membrane and blood priming. No similar episodes were encountered when patients were primed with saline or albumin. The AN-69 membrane is exquisitely pH sensitive. The lower the pH concentration of the blood passing by the membrane, the greater the activation of bradykinin, a known hypotensive-inducing agent, by the dialyzer. On review of blood available from our blood bank, the following parameters became apparent. The pH of standard blood available from our blood bank ranged from 6.1 to 6.4. The blood obtained from our blood bank had significant hyperkalemia, hyponatremia, and hypocalcemia. No reactions were noted when patients were primed with normal saline, which has a pH of around 5.9. We speculate that the presence of endogenous blood substances, such as bradykinin, may have induced the hypotensive episodes. We describe two techniques we developed that should allow for the increased safe and effective use of the AN-69 membranes in continuous venovenous hemodiafiltration circuits. These observations indicate the requirement for careful and close attention to detail when delivering renal replacement therapy to anyone, but especially patients weighing less than 10 kg. © 2001 by the National Kidney Foundation, Inc.