Agonists at the muscle acetylcholine receptor (AChR) can all block the channel as well as activate it. For many partial agonists e.g. choline or tetramethylammonium (TMA), concentrations for activation and block are similar. We recorded cell-attached TMA-activated single-channel currents from HEK293 cells transfected with human nicotinic AChRs (αβδε, transfection ratio 2:1:1:1). In single-channel records at -80 mV, the amplitude of the openings appears to decrease progressively with agonist concentration because of fast channel block. Several records obtained at different TMA concentrations were fitted simultaneously with HJCFIT¹. For TMA the equilibrium constant, K_B, for open channel block was 8.9 ± 0.6 mM, as estimated from the reduction of apparent single-channel amplitude, cf EC₅₀ of 2.2 ± 0.5 mM. If essentially no blockages are detected, the open state and the open-blocked state can be treated as a single compound open state for the purpose of analysing kinetics. Such compound states are indicated by the boxes in Fig 1a and 1b. During fitting, the exit from the compound open state in Fig 1a is given by a transition rate that is not α₂ but rather α₂/(1 + c_B), where c_B = [B]/K_B and [B] is the blocker (agonist) concentration. This reflects the fact that the compound state spends only a fraction of time 1/(1 + c_B) in the state from which exit can occur. Similarly, for the mechanism in Fig 1b, the transition rate for leaving the compound open state via the blocked state (A2F*B) is taken not as α_B but rather α_B c_B/(1 + c_B), i.e. α_B is multiplied by the fraction of time which the compound open state spends in the blocked state. The left column shows a fit with a mechanism that allows block of channels only when they are open. The predicted distribution of apparent open times at the lower concentration (1 mM, Fig 1c) of TMA superimposes on the observations quite well, but at the higher concentration (10 mM, Fig 1e) the prediction is poor. The predominant mean apparent open time is about 1.5 times smaller than is predicted. The right column in Fig 1 shows fit of a mechanism (Fig 1b) in which the block is not selective for the open state, but can occur from any state. In this case the distribution of apparent open times is predicted accurately at both low and high concentrations of TMA. The mean values were α₂ = 2370 s^-1 ± 12% (CVM, n = 4 fits) and α_B = 1550 s^-1 ± 19%, so the channel shuts almost as fast when it is blocked as when it is not. The mean opening transition rate for the unblocked channel was β₂ = 71300 s^-1 ± 9%, similar to that for acetylcholine², and for the blocked channel, the mean opening rate was almost as fast, β_B = 49000 s^-1 ± 9%. Thus TMA seems not act as a pure open channel blocker, but AChRs blocked by TMA can close and return to their resting state without re-opening.