Rhythmogenic pre-Bötzinger complex (preBötC) networks are inspiratory active in brainstem slices that are typically studied in 7-9 mM K(+)instead of physiological extracellular (3 mM) K(+). Also superfusate Ca(2+) is often high (up to 2.4 mM) compared to the most common physiological value (1.2 mM). Because both cations are potent neuromodulators, it is desirable to keep them as close as possible to normal levels for minimizing modulation of the isolated preBötC. We found that modestly raised Ca(2+) depresses preBötC slice rhythm while K(+) elevation counters this inhibition and low Ca(2+) accelerates inspiratory bursting. A Ca(2+) range of 0.75-1 mM and K(+) levels between 4-6 mM may be optimal for long term stable slice rhythm.