The distribution of the desensitization time constant, tauD, of two different, molecular well defined ligand gated receptor channels was analyzed: the embryonic-like nicotinic receptor (nAChR) channel of cultured mouse myotubes and recombinant, homomeric GluR6 receptor channels transiently expressed in HEK293 cells. Experiments were performed using outside-out patches in combination with a system for fast application of agonists which allows solution exchange within 0.1 ms. In response to application of saturating concentrations of acetylcholine (ACh) or glutamate (Glu). the peak current was reached in a submillisecond range and decayed monexponentially in the presence of the agonist, due to desensitization. tauD varied from 10 ms to 100 ms with a mean value of 55.0 +/- 22.6 ms (n = 133) in response to pulses of 10(-4) M ACh for embryonic-like nAChR channels and from 2.6 ms to 8.9 ms with a mean value of 5.0 +/- 1.9 ms (n = 35) in response to pulses of 10(-2) M Glu for homomeric GluR6 receptor channels. The reason for the high variability of the time course of desensitization is at present unclear.