The present study has been performed to test for the influence of serotonin on the potential difference across the cell membrane (PD) of Madin-Darby canine kidney (MDCK)-cells. Under control conditions PD averages -48.6 +/- 0.6 mV (n = 98). Increasing extracellular potassium concentration from 5.4 to 10 and 20 mmol/l depolarizes the cell membrane by +6.3 +/- 0.6 mV (n = 6) and +14.1 +/- 1.0 mV (n = 12), respectively. The cell membrane is transiently hyperpolarized to -67.8 +/- 0.8 mV (n = 63) by 1 mumol/l serotonin. In the presence of serotonin, increasing extracellular potassium concentration from 5.4 to 20 mmol/l depolarizes the cell membrane by +26.4 +/- 1.0 mV (n = 11). 1 mmol/l barium depolarizes the cell membrane by +15.7 +/- 1.3 mV (n = 17) and abolishes the effect of step increases of extracellular potassium concentration from 5.4 to 10 mmol/l. In the presence of barium, serotonin leads to a transient hyperpolarization by -26.3 +/- 1.0 mV (n = 16). During this transient hyperpolarization, the cell membrane is sensitive to extracellular potassium concentration despite the continued presence of barium. 10 mumol/l methysergide hyperpolarize the cell membrane by -7.2 +/- 2.0 mV (n = 6). In the presence of 10 mumol/l methysergide, the effect of serotonin is virtually abolished (+0.4 +/- 0.9 mV, n = 6). 1 mumol/l ketanserin, a 5-HT2 receptor blocking agent, ICS 205-930, a 5-HT3 receptor blocking agent, and phentolamine, an unspecific alpha-receptor blocking agent, do not significantly modify the effect of serotonin. In the nominal absence of extracellular calcium, the effect of serotonin is markedly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)