F508del, the commonest cystic fibrosis (CF) mutation, causes defects in trafficking, stability and gating of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. To rescue these defects, small-molecule correctors and potentiators are being developed. Here we investigate the rescue of F508del-CFTR by the CFTR corrector CF-106951 (C18, CF Foundation Therapeutics compound collection) using inside-out membrane patches from BHK cells expressing wild-type (wt) and F508del-CFTR incubated at 37 °C. As a control, we studied low temperature corrected F508del-CFTR. The pipette (external) solution contained 10 mM Cl- and the bath (internal) solution contained 147 mM Cl-, 1 mM ATP and 75 nM PKA at 37 °C; voltage was -50 mV. The gating behaviour of wt-CFTR is characterized by bursts of openings interrupted by brief closures and separated by longer closures (open probability (Po) = 0.42 ± 0.04, mean burst duration (MBD) = 187 ± 24 ms, interburst interval (IBI) = 155 ± 19 ms, n ≥ 5). In contrast, low temperature (27 °C for 48-72 h) corrected F508del-CFTR is characterized by short bursts of openings separated by prolonged closures (Po = 0.054 ± 0.006, MBD = 95 ± 6 ms, IBI = 1584 ± 149 ms, n ≥ 20). When pre-treated with corrector C18 (5 μM) for 24 h at 37 °C, F508del-CFTR had intermediate bursts of openings separated by shortened long closures (Po = 0.16 ± 0.02, MBD = 140 ± 25 ms, IBI = 894 ± 108 ms, n ≥ 6, p < 0.05, Student’s t-test). When compared with low temperature corrected F508del-CFTR, drug correction caused a three-fold increase in Po by prolonging MBD 47% and reducing IBI 44%. Therefore, C18 is more effective at rescuing F508del-CFTR gating than low temperature incubation. In contrast to wt-CFTR, at 37 °C, F508del-CFTR is unstable and rapidly runs down in excised membrane patches (t1/2 ≈ 2 min). We therefore investigated whether C18 might restore F508del-CFTR stability at 37 °C. Although C18 correction did not eliminate channel run-down, it delayed the complete run-down of F508del-CFTR (t1/2 ≈ 8 min). Like F508del, A561E causes trafficking and severe gating defects (Po = 0.06 ± 0.01, n = 7)1. Upon correction by C18, cell surface expression of A561E-CFTR was observed. However, C18 failed to rescue A561E-CFTR channel gating (Po = 0.04 ± 0.01, n = 9). In summary, the small-molecule corrector C18 restored channel expression, partially rescued F508del-CFTR channel gating and improved stability at the cell surface. The fact that C18 restored channel gating to F508del but not A561E-CFTR suggests that the two mutations might cause trafficking and gating defects by distinct mechanisms.