We tested the hypothesis that a cardiopulmonary bypass prime with lactate would be associated with less acidosis than a prime with only chloride anions because of differences in the measured strong-ion-difference. We randomised 20 patients to a 1500 ml bypass prime with either a chloride-only solution (Ringer's Injection; anions: chloride 152 mmol/l) or a lactated solution (Hartmann's solution; anions: chloride 109 mmol/l, lactate 29 mmol/l). Arterial blood was sampled before bypass and then two, five, 15 and 30 minutes after initiating bypass. We used repeated measures analysis of variance to compare groups. In both groups, the base-excess and measured strong-ion-difference decreased markedly from baseline after two minutes of bypass. The chloride-only group had greater acidosis with lower base-excess and pH (P < 0.05), greatest after five minutes of bypass (C5). Contrary to our hypothesis, however, the difference between the groups was not due to a difference in the measured strong-ion-difference, P = 0.88. At C5 when the difference in standard base-excess between the groups was greatest, 1.9 mmol/l (95% confidence interval: 0.1 to 3.6 mmol/l, P < 0.05), the difference in the measured strong-ion-difference was only 0.2 mmol/l (95% confidence interval: -2.4 to 2.7 mmol/l, P > 0.05). There was, however a difference in the net-unmeasured-ions (strong-ion-gap). We conclude that acid-base changes with cardiopulmonary bypass may differ with the prime but that the early differences between chloride-only and lactated primes appear not to be due to differences in the measured strong-ion-difference. We suggest future studies examine other possible mechanisms including unmeasured ions.