A directive from the Food and Drug Administration indicates that the use of plasma protein fraction (PPF) is contraindicated during cardiopulmonary bypass because of possible hypotension. Bradykinin has been implicated as the cause of this hypotension. Bradykinin levels were measured by radioimmunoassay in PPF and in 5% albumin and were found to be consistently elevated in the former and occasionally in the latter. The addition of PPF to pump primes resulted in significantly elevated levels of bradykinin, which rapidly cleared, indicating that extrapulmonary sites of bradykinin inactivation were efficient. The potential hypotensive effect of PPF was observed by determining the change in mean perfusion pressure in two groups of patients: one group with a 3,000 ml crystalloid prime and the other with a prime of 2,000 ml of crystalloid and 1,000 ml of PPF. There was no significant difference in the perfusion pressure between the two groups at any point, and the hypotensive effects seen in both groups were readily treated, suggesting that the directive against the use of PPF during cardiopulmonary bypass may be unnecessarily restrictive.