BACKGROUND: Current-generation multichannel blood gas electrolyte analyzer systems (MBGES) have the ability to measure blood gases & electrolytes simultaneously. The proposed volume of sample required to achieve this is as little as 1.8 mL. Previous studies have identified inaccuracies & imprecision of blood gas and electrolyte results caused by anticoagulants & small sample size. However, the effects of these two variables on measured analyte parameters have not been addressed for simultaneous measurements on current-generation MBGES. We designed a prospective study to quantify errors introduced into blood gas & electrolyte measurements by sample size & concentration of dry lyophilized heparin during simultaneous analysis using a Corning 288 MBGES. METHODS: Arterial blood was collected from an arterially cannulated 33-year-old healthy Caucasian man. Seventy samples of blood were removed, comprising 10 randomly ordered sets of 0.2, 0.4, 0.6, 0.8, 1.0, 2.0, & 3.0 mL of blood; the resulting specimens contained ∼ 250, 125, 83, 63, 50, 25, & 17 IU of lithium heparin to 1.0 mL of blood, respectively. Sodium, potassium, ionized calcium, pH, PaO2, PaCO2, & total hemoglobin were all measured according to criterion standard for arterial blood gas analysis, collection, & calibration. RESULTS: Using analysis of variance & the Scheffe test, small sample volumes/high heparin concentrations resulted in lower sodium (p < 0.001) & ionized calcium (p < 0.001) and higher PaO2 (p = 0.03) values. No variations were found in potassium, PaCO2, or total hemoglobin. Sodium & ionized calcium concentrations are underestimated in sample volumes of < 0.6 mL with lithium heparin concentrations > 83 IU/mL. CONCLUSION: When standard samples are used with MBGES, we recommend a minimum 0.6-mL sample size for accurate & precise blood gas & electrolyte values.