5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) is an indolealkylamine which has agonist activity at 5HT receptors. In the present investigation, 5-MeODMT had two types of effects on medullary respiratory neurons of the cat. Iontophoretic administration or i.v. doses (43 +/- 8.9 micrograms/kg) of 5-MeODMT hyperpolarized respiratory neurons and severely reduced action potential discharges. Cinanserin, a 5HT-2/1 c receptor antagonist, when injected i.v. reduced the inhibition produced by i.v. injection of 5-MeODMT. Iontophoresis of cinanserin did not antagonize inhibition produced by iontophoresis of 5-MeODMT or 5-HT. The depression of respiratory discharge by i.v. injection of 5-MeODMT is attributed to presynaptic effects (network depression) and post-synaptic activation of 5HT-1A receptors on respiratory neurons. 5-MeODMT (27 +/- 2.78 micrograms/kg i.v.) also increased discharge frequency of inspiratory and expiratory neurons. Inspiratory neuron discharges were briefer and expiratory neuron discharges occurred earlier in relation to phrenic nerve activity. It is suggested that the effects of the smaller doses are due to binding of 5-MeODMT to 5HT-1A receptors on early inspiratory neurons of the medulla.