1. Whole-cell (ICa) and single Ca2+ channel currents were measured in inspiratory neurones of neonatal mice (4-12 days old). During whole-cell recordings, ICa slowly declined and disappeared within 10-20 min. The run-down was delayed during hypoxia, indicating ICa potentiation. 2. Ca2+ channels were recorded in cell-attached patches using pipettes which contained 110 mM Ba2+. L-type Ca2+ channels exhibited a non-ohmic I-V relationship. The slope conductance was 24 pS below and 50 pS above their null potential. The open probability of the channels increased during oxygen depletion, reaching a maximum 2 min after the onset of hypoxia. Restoration of the oxygen supply brought the channel activity back to initial levels. 3. The channel activity was enhanced by 3-30 microM S(-)Bay K 8644, an agonist of L-type Ca2+ channels. The open probability was increased about 3-fold and the activation curve was shifted by 20 mV in the hyperpolarizing direction. In the presence of the agonist, channel open time increased and long openings appeared. Agonist-modulated channels were also potentiated during oxygen depletion. The effect was due to an increase in open time and a decrease in closed time. The channels were inhibited by bath application of nifedipine (10 microM) and nitrendipine (20 microM). 4. Weak bases such as NH4Cl and TMA increased and weak acids such as sodium acetate and propionate decreased activity of the channels, indicating that they are modulated by intracellular pH. Bath application of 1 microM forskolin enhanced the channel activity, whereas 500 microM NaF suppressed it. 5. L-type Ca2+ channels were modulated by an agonist for mGluR1/5 receptors, (S)-3, 5-dihydrophenylglycine (DHPG, 5 microM). In its presence, the hypoxic facilitation of channels was abolished. 6. After blockade of L-type Ca2+ channels, the respiratory response to hypoxia was modified. The transient enhancement of the respiratory rhythm (augmentation) was no longer evident and the secondary depression occurred earlier. 7. We suggest that L-type Ca2+ channels contribute to the early hypoxic response of the respiratory centre. Glutamate release during hypoxia stimulates postsynaptic metabotropic glutamate receptors, which activate the Ca2+ channels.