The effects of velnacrine (1-hydroxytacrine), tacrine and physostigmine on indirectly elicited twitch at low and high stimulation frequencies were analyzed in the rat phrenic hemidiaphragm preparation. At 0.2 Hz, velnacrine and physostigmine behaved in a similar manner, the latter showing a higher potentiating effect. This potentiation was observed at 3–100 μM velnacrine, whereas a slight depression appeared at higher concentrations. When tetanic responses were studied, the drug concentrations needed to depress tetanic tension and tetanic fade were quite different in the case of velnacrine (depression of tetanic tension from 1 μM and tetanic fade from 170 μM), whereas physostigmine and tacrine were able to affect these parameters at very similar concentrations. The results suggest that some effects of velnacrine could differ from those of tacrine in spite of the chemical similarity.