Embryonic-like nicotinic channels were studied in mouse myotubes. Channel currents were measured by patch-clamping outside-out excised patches to which pulses of agonists and drugs could be applied by a liquid filament switch. The holding potential of the patches was generally around 40 mV. Pulses of 10(-4) M acetylcholine elicited average channel currents which reached a peak open probability, P(o,peak,) of 0.93 within 0.5 ms and decayed with a time constant of desensitization of 20-80 ms. When physostigmine (10(-5) to 10(-3) M) or procaine (3 x 10(-5) to 10(-3) M) was added to the acetylcholine pulses, a fast decay component of the current appeared which shortened to a time constant of 0.5 ms for the maximal drug concentrations. The fast decay was followed by a slow one which declined in amplitude with increasing concentrations of the drugs. After the end of pulses of 10 M acetylcholine plus 3 x 10(-4) M physostigmine the average current rose again, reaching a peak with approximately 5 ms delay, and then decayed slowly. The amplitude of this recovery current was approximately 0.4 P(o,peak) after 5 ms pulses and decreased with increasing pulse duration due to desensitization. The results can be quantitatively modelled based on a circular reaction scheme involving desensitization. Physostigmine and procaine bind to the open state to cause channel block. Also, the blocked channel was subject to desensitization. The rate constants of block were 6 x 10(6) M(-1) s(-1) for physostigmine and 2 x 10(6) M(-1) s(-1) for procaine, and the rate of unblocking was 200 s(-1) for both blockers (at -40 mV and 20 degrees C).