Whole-cell patch-clamp measurements indicate that human small-cell lung cancer (SCLC) cells express voltage-dependent potassium channels, whose function is blocked by K+ channel antagonist 4-aminopyridine (4-AP). Exposure of the tumour cells to 4 mM 4-AP reduced the peak outward K+ current (evoked by a depolarization to +80 mV) from 2.05 +/- 0.24 nA (mean +/- SEM, n = 28 cells) to 0.98 +/- 0.12 nA (n = 27). Incubation of SCL cells with 0.1, 4 and 16 mM 4-AP resulted in a concentration- and time-dependent reduction in the number of viable cells when compared with the control; over a period of 144 hours, the drug either significantly reduced the number of viable SCLC cells or caused an apparent cessation of neoplastic cell proliferation, whereas the untreated control cells demonstrated a more than 16-fold multiplication in the number of viable cells. The inhibitory effect on cell growth was also observed with an additional K+ channel antagonist, tetraethylammonium. These data suggest that voltage-activated K+ channels expressed by SCLC cells play a role in neoplastic cell proliferation.